UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16 UNDER THE SECURITIES EXCHANGE ACT OF 1934
October 10, 2024
Commission File Number: 001-39363
IMMATICS N.V.
Paul-Ehrlich-Straße 15
72076 Tübingen, Federal Republic of Germany
(Address of principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:
| Form 20-F | ☒ |
Form 40-F | ☐ |
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
On October 10, 2024, Immatics N.V. (the “Company” or “Immatics”) provided updated Phase 1b clinical data on ACTengine® IMA203 TCR-T targeting PRAME in melanoma patients and provided an update on SUPRAME, the upcoming Phase 3 trial to evaluate IMA203 in metastatic melanoma patients. IMA203 is Immatics’ most advanced TCR-based autologous cell therapy that is directed against an HLA-A*02-presented (human leukocyte antigen) peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers. The data cutoff was August 23, 2024.
Patient Baseline Characteristics. As of data cutoff, 28 heavily pretreated patients with metastatic melanoma were treated with IMA203 at the recommended Phase 2 dose (“RP2D”) of 1 to 10 billion total TCR-T cells during the Phase 1b dose expansion part of the clinical trial. The treated patient population is composed of patients with a median of 2 lines of prior systemic treatments, consisting of cutaneous melanoma patients (N=13), uveal melanoma patients (N=12), mucosal melanoma patients (N=2) and a patient with melanoma of unknown primary (N=1).
Safety Data. The safety population includes 701 patients in the Phase 1a dose escalation and Phase 1b dose expansion parts of the trial across all dose levels and all tumor types. Grade ≥3 treatment-emergent adverse events (“TEAEs”) were observed in all patients. As shown in the table below, the most frequent adverse events were expected cytopenias (Grade 1-4) associated with lymphodepletion as well as mostly mild to moderate cytokine release syndrome (“CRS”). Some patients infrequently experienced immune effector cell-associated neurotoxicity syndrome (“ICANS’) (Grade 1: 6% of patients, Grade 2: 4% of patients, Grade 3: 4% of patients). No Grade 5 treatment-related adverse events were observed in the safety population, even at doses up to ~10x109 TCR-T cells. The tolerability profile in the Phase 1b melanoma subset is generally consistent with the full IMA203 monotherapy tolerability profile.
1 All patients who started lymphodepletion. Includes one patient who started lymphodepletion but did not receive IMA203 TCR-T cells and one patient who started lymphodepletion with T cell infusion scheduled after the data cutoff.
Treatment-Emergent Adverse Events in the Safety Population (N=701)
All TEAEs with ≥ Grade 3 regardless of relatedness to study treatment. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 5.0. Grades for CRS and ICANS were determined according to CARTOX criteria (Neelapu et al., 2019). Patients are counted only once per adverse event and severity classification. Based on interim data extracted from open clinical database (23-Aug-2024);
1 Two patients with disease progression after first IMA203 infusion received exploratory second IMA203 infusion. They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table: First patient: Abdominal pain, Cytokine release syndrome, Diarrhoea, Hypokalaemia, Proteinuria; Second patient: Humerus fracture, Muscle spasms, Neutropenia, Thrombocytopenia; 2 ICANS: Immune effector cell-associated neurotoxicity syndrome; 3 Fatal Adverse events were not considered related to any study drug; 4 Patient died from sepsis of unknown origin and did not receive IMA203 TCR-T cells; 5 DLT: Dose limiting toxicity in phase 1a at DL2 reported on March 17, 2021.
Anti-tumor Activity and Durability. The table below sets forth the observed anti-tumor activity of IMA203 and durability of responses in all melanoma patients in the Phase 1b clinical trial and in cutaneous melanoma patients in the Phase 1b clinical trial. In the melanoma patient population, 7 of the 14 confirmed responses were ongoing as of
data cutoff. For this analysis, the median follow-up for the median duration of response was 9.3 months compared to 3.5 months from the most recent data update in May 2024.
| All melanoma patients in Phase 1b (N=282,3) | Cutaneous melanoma patients in Phase 1b (N=13 3) | |
| Confirmed Objective Response Rate | 54% (14/26) | 54% (7/13) |
| Objective Response Rate | 62% (16/26) | 62% (8/13) |
| Disease Control Rate | 92% (24/26) | 92% (12/13) |
| Tumor Shrinkage | 88% (23/26) | 85% (11/13) |
| Median Duration of Response | 12.1 months | 12.1 months |
| Median Progression-Free Survival | 6.0 months | 6.1 months |
| Median Overall Survival | Not reached | 15.9 months |
Response Over Time of IMA203 in Melanoma (N=28 2, 3)
Progression-Free Survival (“PFS”) and Overall Survival (“OS”). Manufacturing improvements were implemented prior to the Phase 1b part of the trial to enhance key features of IMA203. As a result, all patients in dose expansion were treated with an updated version of IMA203 that includes a T cell enrichment process using monocyte depletion (negative selection) or CD8/CD4 positive selection. The updated data demonstrate a significant positive shift in median PFS and median OS between melanoma patients treated during Phase 1a and patients treated in Phase 1b, which is shown in the table below.
| Phase 1b dose expansion melanoma patients (N=28) | Phase 1a dose escalation melanoma patients (N=11) | |
| Median Progression-Free Survival | 6.0 months | 2.6 months |
| Median Overall Survival | Not reached | 6.3 months |
In addition, approximately half of all patients in the Phase 1b trial have a deep response (>50% tumor reduction). This subgroup of patients was observed to have a median PFS of more than 1 year, while patients with <50% tumor
2 First tumor assessment post infusion pending for additional two melanoma patients at data cutoff.
3 Melanoma efficacy population excludes 5 patients treated at DL4 in Phase 1a of the trial as reported in the May 2024 update, based on different manufacturing version used that affects the T cell product.
reduction (including patients with tumor size increase) were still observed with a more than 2 times longer median PFS compared to patients treated in dose escalation with suboptimal doses.
Translational Data. Translational data from patients across Phase 1a and Phase 1b indicate that IMA203 T cells rapidly engrafted in all patients after a single dose and show a persistence of more than two years. Three associations/correlations were observed demonstrating high consistency of dose exposure, biological data and clinical outcome in all patients treated with IMA203 for which samples were available (N=65): First, IMA203 T cell dose is significantly associated with confirmed clinical responses (p=0.02). Second, IMA203 T cell dose is correlated with T cell peak level (cmax, r=0.84, p=1.6x10-18). Third, IMA203 T cell peak level (cmax, p=0.05) and T cell exposure (AUC0-28d, p=0.05) are associated with confirmed clinical responses.
Development Path and Manufacturing for IMA203 Monotherapy. On September 24, 2024, Immatics completed a Type D meeting with the U.S. Food and Drug Administration (“FDA”) to confirm RP2D and the chemistry, manufacturing and controls (“CMC”) package as well as discuss the trial design for SUPRAME, the planned registration-enabling Phase 3 randomized-controlled clinical trial for IMA203. Written post-meeting minutes from the FDA have been received.
SUPRAME will evaluate IMA203 targeting PRAME in 360 HLA-A*02:01-positive patients with second-line or later (2L+) unresectable or metastatic melanoma who have received prior treatment with a checkpoint inhibitor. Patients will be randomized 1:1 for IMA203 or investigator’s choice of selected approved treatments in the 2L+ setting. Based on the Company’s discussions with the FDA, the primary endpoint for full approval will be median PFS. Given the expected PFS of 2-3 months in this patient population, as well as the PFS of 6 months observed in the data from the IMA203 Phase 1b trial, the Company has determined that utilizing median PFS as the primary endpoint is the fastest pathway to seeking full approval and presents a more attractive commercial positioning as compared to objective response rate (“ORR”). Secondary endpoints for the trial will include ORR, safety, duration of response, no overall survival detriment and patient-reported outcomes. A pre-specified interim analysis is planned for early 2026.
The SUPRAME Phase 3 trial is planned to run globally with sites in the United States and Europe with the initial goal of seeking Biologics License Application (“BLA”) approval in the United States. On October 2, 2024, Immatics also completed a meeting with the Paul Ehrlich Institute (PEI), the German regulatory authority, and determined the same trial design for conducting the clinical trial in Germany.
The SUPRAME Phase 3 trial is on track to commence in December 2024 and patient enrolment is forecasted to be completed in 2026. The Company aims to submit a BLA in early 2027 for full approval.
Immatics’ late-stage clinical cell therapy development is supported by its differentiated manufacturing related to timeline, capabilities and facilities. IMA203 cell therapy products are manufactured within 7 days, followed by a 7-day QC release testing at a success rate of >95% to reach the target dose. The Company has also completed construction of a ~100,000 square foot research and development and good manufacturing practices (“GMP”) manufacturing facility with a modular design for efficient and cost-effective scalability intended to serve early-stage and registration-enabling trials, as well as commercial supply. The new site is expected to start GMP manufacturing of cell therapy products in early 2025. Meanwhile, the existing GMP facility, which is run in collaboration with UT Health, will remain active until the end of 2025.
* * *
In connection with the foregoing, the Company issued a press release, a copy of which is attached hereto as Exhibit 99.1, and provided a presentation, a copy of which is attached hereto as Exhibit 99.2, and made available an updated corporate presentation, a copy of which is attached hereto as Exhibit 99.3.
Certain statements in this report may be considered forward-looking statements. Forward-looking statements generally relate to future events or the Company’s future financial or operating performance. For example, statements concerning timing of data read-outs for product candidates, the timing, outcome and design of clinical trials, the nature of clinical trials (including whether such clinical trials will be registration-enabling), the timing of IND or CTA filing for pre-clinical stage product candidates, the timing of BLA filings for clinical stage product candidates, estimated market opportunities of product candidates, manufacturing timetables, capacity and success
rates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “plan”, “target”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Immatics and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management’s control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission (SEC). Nothing in this report should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. The Company undertakes no duty to update these forward-looking statements. All the scientific and clinical data presented within this report are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification.
INCORPORATION BY REFERENCE
This Report on Form 6-K (other than Exhibits 99.1, 99.2 and 99.3 hereto) shall be deemed to be incorporated by reference into the registration statements on Form F-3 (Registration Nos. 333-240260 and 333-274218) of Immatics N.V. and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.
EXHIBIT INDEX
| Exhibit No. | Description |
| 99.1 | Press release dated October 10, 2024 |
| 99.2 | Presentation dated October 10, 2024 |
| 99.3 | Corporate presentation dated October 10, 2024 |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| IMMATICS N.V. | ||
| Date: October 10, 2024 | ||
| By: | /s/ Harpreet Singh | |
| Name: | Harpreet Singh | |
| Title: | Chief Executive Officer | |
Exhibit 99.1
PRESS RELEASE
Immatics Announces
Updated Phase 1b Clinical Data on
ACTengine® IMA203 TCR-T Targeting PRAME in Melanoma Patients and
Provides Update on Upcoming SUPRAME Phase 3 Trial
Company to host conference call and webcast today, October 10, at 9:00 am EDT/3:00 pm CEST
| · | Company announces updated Phase 1b clinical data on ACTengine® IMA203 targeting PRAME in 28 heavily pretreated metastatic melanoma patients with substantially enhanced maturity compared to the last data update in May 2024 and provides the first report on progression-free survival (PFS) and overall survival (OS) |
| · | Based on the Phase 1b data, the Company will proceed directly to a registration-enabling Phase 3 trial |
| · | Regulatory pathway and clinical trial design for IMA203 finalized following FDA Type D meetings and meeting with the Paul Ehrlich Institute (PEI); RP2D and CMC package confirmed |
| · | IMA203 continues to maintain a favorable tolerability profile in patients in Phase 1a and Phase 1b treated across all dose levels |
| · | IMA203 demonstrates a confirmed objective response rate of 54% with median duration of response of 12.1 months in Phase 1b |
| · | Median PFS is 6 months, comparing favorably to the IMA203 Phase 1a dose escalation median PFS of 2.6 months; patients with deep responses show median PFS of more than one year; median OS not reached |
| · | Phase 3 trial, “SUPRAME,” will enroll 360 patients with unresectable or metastatic melanoma post treatment with a checkpoint inhibitor (2L+) and will randomize patients 1:1 for treatment with IMA203 or investigator’s choice |
| · | Primary endpoint for full approval will be median PFS, which constitutes the fastest pathway to registration in this patient population |
| Immatics Press Release October 10, 2024 | 1 | 8 |
| · | SUPRAME Phase 3 trial is on track to commence in December 2024; enrollment forecasted to be completed in 2026 with a pre-specified interim analysis planned for early 2026 |
| · | Conference call and webcast can be accessed here |
Houston, Texas and Tuebingen, Germany, October 10, 2024 – Immatics N.V. (NASDAQ: IMTX, “Immatics” or the “Company”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced updated Phase 1b clinical data on ACTengine® IMA203 TCR-T targeting PRAME in melanoma patients and provided an update on SUPRAME, the upcoming Phase 3 trial to evaluate IMA203 in metastatic melanoma patients.
The data from the ongoing Phase 1b trial will be presented on Friday, October 11, 2024, by Martin Wermke, M.D., during Plenary Session 1, Developmental Immunotherapy (Cellular Immunotherapy, Vaccines, & New Checkpoints) at the Society for Melanoma Research Congress 2024. The IMA203 data slides are accessible in the ‘Events & Presentations’ section of the Investor & Media section of the Company’s website. The conference presentation will include additional patient cases.
“Observing significant tumor shrinkage and durable responses combined with meaningful progression-free survival and overall survival outcomes after a single treatment with ACTengine® IMA203 in this patient population that have all exhausted multiple lines of systemic treatments illustrates the impact IMA203 can have on metastatic melanoma patients,” said Martin Wermke, M.D., Coordinating Investigator of the ACTengine® IMA203 TCR-T trial. “These results now affirm the therapeutic potential of IMA203 and provide a strong rationale for the expedited late-stage clinical development of this product candidate.”
“We are enthusiastic about the clinical data as they confirm our conviction in the durability and long-term efficacy of ACTengine® IMA203, demonstrated by the favorable median progression-free survival for patients in the dose expansion cohort. I would like to highlight that a subgroup of 12 out of 26 patients showed more than 50% reduction of tumor lesions and a median PFS of 13.4 months,” said Cedrik Britten, M.D., Chief Medical Officer at Immatics. “We believe the presentation of this data set in conjunction with our recent meeting with the FDA, which has resulted in a pivotal trial design with progression-free survival as the primary endpoint for full approval, positions us to advance the development of IMA203 in the second-line or later metastatic melanoma setting.”
Patient Population and Clinical Data Summary - ACTengine® IMA203 Monotherapy Phase 1b Trial
| Immatics Press Release October 10, 2024 | 2 | 8 |
Patient population: Heavily pretreated metastatic melanoma patients
As of August 23, 2024, 28 heavily pretreated patients with metastatic melanoma were treated at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells) with IMA203 during the Phase 1b dose expansion part of the clinical trial. The treated patient population is composed of patients with a median of 2 lines of prior systemic treatments, consisting of cutaneous melanoma patients (N=13), uveal melanoma patients (N=12), mucosal melanoma patients (N=2) and a patient with melanoma of unknown primary (N=1).
Safety: Favorable tolerability profile demonstrated across all dose levels in Phase 1a and Phase 1b
IMA203 monotherapy has maintained a favorable tolerability profile with no treatment-related Grade 5 adverse events in the safety population (N=701 Phase 1a and Phase 1b patients across all dose levels and all tumor types), even at doses up to ~10x109 TCR-T cells.
The most frequent adverse events were expected cytopenias (Grade 1 – 4) associated with lymphodepletion as well as mostly mild to moderate cytokine release syndrome (CRS). Some patients infrequently experienced ICANS (Grade 1: 6%, Grade 2: 4%, Grade 3: 4%).
The full IMA203 monotherapy tolerability profile is also generally consistent with that observed in the Phase 1b melanoma subset.
Anti-tumor activity and durability: Durable objective responses in melanoma patients at RP2D3
This data update
adds substantial maturity to the most recent data update from May 2024 (data cut-off on April 25, 2024). The median follow-up for the
median duration of response for this analysis was 9.3 months compared to 3.5 months in May 2024.
1 All patients who started lymphodepletion. Includes one patient who started lymphodepletion but did not receive IMA203 TCR-T cells and one patient who started lymphodepletion with T cell infusion scheduled after data-cut.
| Immatics Press Release October 10, 2024 | 3 | 8 |
All melanoma patients in Phase 1b (N=282,3) |
Cutaneous melanoma patients in Phase 1b (N=133) | |
| Confirmed Objective Response Rate | 54% (14/26) | 54% (7/13) |
| Objective Response Rate | 62% (16/26) | 62% (8/13) |
| Disease Control Rate | 92% (24/26) | 92% (12/13) |
| Tumor Shrinkage | 88% (23/26) | 85% (11/13) |
| Median Duration of Response | 12.1 months | 12.1 months |
| Median Progression-Free Survival | 6.0 months | 6.1 months |
| Median Overall Survival | Not reached | 15.9 months |
Progression-free survival (PFS) and overall survival (OS): Significant shift in PFS and OS between Phase 1a dose escalation to Phase 1b dose expansion in melanoma patients
Manufacturing improvements were implemented prior to the Phase 1b part of the trial to enhance key features of IMA203. As a result, all patients in dose expansion were treated with an updated version of IMA203 that includes a T cell enrichment process using monocyte depletion (negative selection) or CD8/CD4 positive selection.
The data presented today demonstrate a significant positive shift in median PFS and median OS between melanoma patients treated during Phase 1a and patients treated in Phase 1b.
Phase 1b dose expansion melanoma patients (N=28) |
Phase 1a dose escalation melanoma patients (N=11) | |
| Median Progression-free Survival | 6.0 months | 2.6 months |
| Median Overall Survival | Not reached | 6.3 months |
2 First tumor assessment post infusion pending for additional two melanoma patients at data-cut.
3 Melanoma efficacy population excludes 5 patients treated at DL4 in Phase 1a of the trial as reported in the May 2024 update, based on different manufacturing version used that affects the T cell product. See the IMA203 data presentation slides available on the Immatics website for more detailed information and a patient population flow chart.
| Immatics Press Release October 10, 2024 | 4 | 8 |
In addition, approximately half of all patients in the Phase 1b trial have a deep response (>50% tumor reduction). This subgroup of patients was observed to have a median PFS of more than one year, while patients with <50% tumor reduction (including patients with tumor size increase) were still observed with a more than 2 times longer median PFS compared to patients treated in dose escalation with suboptimal doses.
Translational data: IMA203 T cell dose and T cell exposure are associated with clinical responses
Translational data from patients across Phase 1a and Phase 1b indicate that IMA203 T cells rapidly engrafted in all patients after a single dose and show a persistence of more than two years. Three associations/correlations were observed demonstrating high consistency of dose exposure, biological data and clinical outcome in all patients treated with IMA203 for which samples were available (N=65):
| 1. | IMA203 T cell dose is significantly associated with confirmed clinical responses (p=0.02), |
| 2. | IMA203 T cell dose is correlated with T cell peak level (cmax, r=0.84, p=1.6x10-18), |
| 3. | IMA203 T cell peak level (cmax, p=0.05) and T cell exposure (AUC0-28d, p=0.05) are associated with confirmed clinical responses. |
Development Path and Manufacturing for ACTengine® IMA203 Monotherapy
On September 24, 2024, Immatics completed a Type D meeting with the U.S. Food and Drug Administration (FDA) to confirm RP2D and the CMC package as well as discuss the trial design for SUPRAME, the planned registration-enabling Phase 3 randomized-controlled clinical trial for IMA203. Written post-meeting minutes from the FDA have been received.
The Phase 3 trial will evaluate IMA203 targeting PRAME in 360 HLA-A*02:01-positive patients with second-line or later (2L+) unresectable or metastatic melanoma who have received prior treatment with a checkpoint inhibitor. Patients will be randomized 1:1 for IMA203 or investigator’s choice of selected approved treatments in the 2L+ setting.
Based on the Company’s discussions with the FDA, the primary endpoint for full approval will be median PFS. Given the expected PFS of 2-3 months4 in this patient population, as well as the PFS of 6 months observed in the data from the IMA203 Phase 1b trial, the Company has determined that utilizing median PFS as the primary endpoint is the fastest pathway to seeking full approval and presents a more attractive commercial positioning as
4 See the IMA203 data presentation slides available on the Immatics website for more detailed information and an overview of studies.
| Immatics Press Release October 10, 2024 | 5 | 8 |
compared to objective response rate (ORR). Secondary endpoints for the trial will include ORR, safety, duration of response, no overall survival detriment and patient-reported outcomes. A pre-specified interim analysis is planned for early 2026.
The SUPRAME Phase 3 trial is planned to run globally with sites in the United States and Europe with the initial goal of seeking Biologics License Application (BLA) approval in the United States. On October 2, 2024, Immatics also completed a meeting with the Paul Ehrlich Institute (PEI), the German regulatory authority, and determined the same trial design for conducting the clinical trial in Germany.
The Phase 3 trial is on track to commence in December 2024 and patient enrollment is forecasted to be completed in 2026. The Company aims to submit a BLA in early 2027 for full approval.
Immatics’ late-stage clinical cell therapy development is supported by its differentiated manufacturing related to timeline, capabilities and facilities. ACTengine® IMA203 cell therapy products are manufactured within 7 days, followed by a 7-day QC release testing at a success rate of >95% to reach the target dose. The Company has also completed construction of a ~100,000 square foot R&D and GMP manufacturing facility with a modular design for efficient and cost-effective scalability intended to serve early-stage and registration-enabling trials, as well as commercial supply. The new site is expected to start GMP manufacturing of cell therapy products in early 2025. Meanwhile, the existing GMP facility, which is run in collaboration with UT Health, will remain active until YE 2025
Immatics Conference Call and Webcast
Immatics will host a conference call and webcast today, October 10, 2024, at 9:00 am EDT/3:00 pm CEST to discuss the clinical data.
A replay of the webcast will be made available shortly after the conclusion of the call and archived on the Immatics website for at least 90 days.
About ACTengine® IMA203 and Target PRAME
ACTengine® IMA203 is Immatics’ most advanced TCR-based autologous cell therapy that is directed against an HLA-A*02-presented (human leukocyte antigen) peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers. PRAME is homogeneously and specifically expressed in tumor tissue and Immatics’ PRAME peptide is present at a high copy number per tumor cell. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform, XPRESIDENT®. Through its proprietary TCR discovery and engineering platform
| Immatics Press Release October 10, 2024 | 6 | 8 |
XCEPTOR®, Immatics has generated a highly specific T cell receptor (TCR) against this target for ACTengine® IMA203.
ACTengine® IMA203 TCR-T is currently being evaluated as a monotherapy in a Phase 1 clinical trial in patients with solid tumors expressing PRAME, such as cutaneous melanoma. An IMA203 registration-enabling randomized controlled Phase 3 trial, “SUPRAME,” is planned to commence in December 2024.
ACTengine® IMA203 TCR-T is also currently being evaluated in Phase 1 IMA203CD8 (GEN2) monotherapy, where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor.
- END -
About Immatics
Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.
Immatics intends to use its website www.immatics.com as a means of disclosing material non-public information. For regular updates you can also follow us on X, Instagram and LinkedIn.
Forward-Looking Statements
Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or the Company’s future financial or operating performance. For example, statements concerning timing of data read-outs for product candidates, the timing, outcome and design of clinical trials, the nature of clinical trials (including whether such clinical trials will be registration-enabling), the timing of IND or CTA filing for pre-clinical stage product candidates, the timing of BLA filings for clinical stage product candidates, estimated market opportunities of product candidates, manufacturing timetables, capacity and success rates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “plan”, “target”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking
| Immatics Press Release October 10, 2024 | 7 | 8 |
statements are based upon estimates and assumptions that, while considered reasonable by Immatics and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission (SEC). Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. The Company undertakes no duty to update these forward-looking statements. All the scientific and clinical data presented within this press release are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification.
For more information, please contact:
| Media | |
| Trophic Communications | |
| Phone: +49 171 3512733 | |
| immatics@trophic.eu |
| Immatics N.V. | |
| Jordan Silverstein | |
| Head of Strategy | |
| Phone: +1 346 319-3325 | |
| InvestorRelations@immatics.com |
| Immatics Press Release October 10, 2024 | 8 | 8 |
Exhibit 99.2
ACTengine® IMA203 TCR - T Targeting PRAME in PD1 Refractory Metastatic Melanoma - Phase 1b Dose Expansion Clinical Data Update October 10, 2024 Oral presentation by Martin Wermke at the Society of Melanoma Research Congress on October 11, 2024 Data cut - off Aug 23, 2024 Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution.
Forward - Looking Statement This presentation (“Presentation”) is provided by Immatics N . V . (“Immatics” or the “Company”) for informational purposes only . The information contained herein does not purport to be all - inclusive and none of Immatics, any of its affiliates, any of its or their respective control persons, officers, directors, employees or representatives makes any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation . Forward - Looking Statements . Certain statements in this presentation may be considered forward - looking statements . Forward - looking statements generally relate to future events or the Company’s future financial or operating performance . For example, statements concerning timing of data read - outs for product candidates, the timing, outcome and design of clinical trials, the nature of clinical trials (including whether such clinical trials will be registration - enabling), the timing of IND or CTA filing for pre - clinical stage product candidates, the timing of BLA filings for clinical stage product candidates, estimated market opportunities of product candidates, manufacturing timetables, capacity and success rates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward - looking statements . In some cases, you can identify forward - looking statements by terminology such as “may”, “should”, “expect”, “plan”, “target”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology . Such forward - looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements . These forward - looking statements are based upon estimates and assumptions that, while considered reasonable by Immatics and its management, are inherently uncertain . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual Report on Form 20 - F and other filings with the Securities and Exchange Commission (SEC) . Nothing in this presentation should be regarded as a representation by any person that the forward - looking statements set forth herein will be achieved or that any of the contemplated results of such forward - looking statements will be achieved . You should not place undue reliance on forward - looking statements, which speak only as of the date they are made . The Company undertakes no duty to update these forward - looking statements . No Offer or Solicitation . This communication is for informational purposes only and does not constitute, or form a part of, an offer to sell or the solicitation of an offer to sell or an offer to buy or the solicitation of an offer to buy any securities, and there shall be no sale of securities, in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction . No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933 , as amended, or in an offering exempt from registration . Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company’s own internal estimates and research . In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions . Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source . All the scientific and clinical data presented within this presentation are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification . 2
PRAME – A Widely Expressed Cancer Testis Antigen 3 100 100 µm 81 90 % PRAME+ cells PRAME RNA Detection in Melanoma Samples (ISH) % PRAME Positive Patients in Selected Indications Uterine Carcinosarcoma Sarcoma Subtypes Uterine Carcinoma Cut. Melanoma Uveal Melanoma 1 Ovarian Carcinoma Squamous NSCLC T NBC Small Cell Lung Cancer 100% 0% 100% 95% up to 100% 95% 90 % 85% 70% 60% 45% Target prevalence based on TCGA (SCLC: in - house) RNAseq data combined with proprietary mass spec - guided RNA expression threshold; 1 Uveal melanoma target prevalence based on IMADetect qPCR testing of screening biopsies from 61 trial patients. ISH: in - situ hybridization Data cut - off Aug 23, 2024
ACTengine® IMA203 TCR - T Monotherapy – Patient Flow 4 HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase Manufacturing by Immatics Infusion of ACTengine® IMA203 TCR - T Product Lymphodepletion * Low dose IL - 2 ** Safety and efficacy monitoring for 12 months Leukapheresis x x Expression Antigen 1 2 3 * 30 mg/m 2 Fludarabine and 500 mg/m 2 Cyclophosphamide for 4 days; ** 1m IU daily days 1 - 5 and twice daily days 6 - 10 Short process time of 14 days 7 - day manufacturing process applying CD8/CD4 T cell selection 7 - day QC release testing 95% (138/146) Cut. Melanoma 89% (54/61) Uveal Melanoma 93% (14/15) Uterine Carcinoma 81% (48/59) Ovarian Carcinoma Target Profiling IMADetect® mRNA assay using Immatics’ MS - guided threshold; Biopsy or archived tissue Patient screening data from Immatics’ clinical trials: Data cut - off Aug 23, 2024
ACTengine® IMA203 TCR - T Trial in Melanoma Heavily Pretreated Patient Population 5 Data cut - off Aug 23, 2024 1 See patient flow in appendix. 2 All infused patients; *Cutaneous melanoma patients had a median of 2 prior lines of checkpoints, see appendix; RP2D: recommended phase 2 dose; CPI: Checkpoint inhibitors; EC1: 0.06 - 0.12x10 9 TCR - T cells/m 2 BSA; DL3: 0.2 - 0.48x10 9 TCR - T cells/m 2 BSA, DL4: 0.2 - 1.2x10 9 TCR - T cells/m 2 BSA, DL5: 1.201 - 4.7x10 9 TCR - T cells/m 2 BSA Melanoma Efficacy Population 2 Melanoma Dose Escalation Population Total Safety P o p ul a t i o n 1 Melanoma (Phase 1b, at RP2D) Mela n o m a (Phase 1a) All Comers (Phase 1a and Phase 1b) N= 2 8 N= 13 N= 12 N= 1 N=2 Total Cutaneous melanoma Uveal melanoma Melanoma of unknown primary Mucosal melanoma N= 1 1 N=8 N=2 N=1 Total Cutaneous melanoma Uveal melanoma Mucosal melanoma N = 7 0 N= 41 N= 29 Total M el an om a Other Number of patients 2 (0, 6) 1* (0, 4) 4 (2, 7) 2 (1, 4) 3 (0, 9) 2 (0, 4) Prior lines of systemic treatment (median, min, max) Thereof CPI (melanoma only) (median, min, max) 60 .7 81 .8 64.3 LDH at baseline >1 x ULN [% of patients] 107.5 (15.0, 309.8) 117.5 (37.0, 211.0) 117.8 (15.0, 309.8) Baseline tumor burden Median Target lesion sum of diameter [mm] (min, max) 82 .1 63 .6 65.7 Liver/brain lesions at baseline [% of patients] DL4/5 EC1/DL3/4 DL1 - 5 Dose level 4.1 (1.3, 10.2) 0.586 (0.10, 2.09) 2.09 (0.08, 10.2) Total infused dose TCR - T cells [x10 9 ] Melanoma Efficacy Population 2 (N=28) Melanoma Patients in Phase 1b Dose Expansion RP2D defined at 1 - 10x10 9 TCR - T cells (DL4/5) Total Safety Population 1 (N=70) Phase 1a Dose Escalation Dose Level 1 - 4 (total safety pop. N=28) Phase 1b Dose Expansion Dose Level 4/5 (total safety pop. N=42)
6 Data cut - off Aug 23, 2024 • Most frequent adverse events were expected cytopenias (Grade 1 - 4) associated with lymphodepletion in all patients • Mostly mild to moderate cytokine release syndrome (CRS) • 37% (26/70) Grade 1 • 46% (32/70) Grade 2 • 11% (8/70) Grade 3 2 • Infrequent ICANS (6% Grade 1, 4% Grade 2, 4% Grade 3) • No IMA203 - related deaths • Full IMA203 monotherapy tolerability profile is available in appendix • Tolerability in the melanoma subset is generally consistent with the full IMA203 monotherapy tolerability profile 1 See patient flow in appendix; 2 One grade 3 CRS only after exploratory second infusion; CRS and ICANS graded by CARTOX criteria (Neelapu et al ., 2019); ICANS: Immune Effector Cell - Associated Neurotoxicity Syndrome. Most Frequent Adverse Events of IMA203 Across All Dose Levels in Phase 1a/b N=70 Patients in Total Safety Population 1 Favorable tolerability profile for IMA203 monotherapy at recommended phase 2 dose (1x10 9 to 10x10 9 TCR - T cells)
Best Overall Response for IMA203 in Melanoma Objective Responses in Heavily Pretreated Patients in Phase 1b (N=28 # ) 7 Data cut - off Aug 23, 2024 ongoi n g # First tumor assessment post infusion pending for two melanoma patients at data - cut; * Maximum change of target lesions and RECIST1.1 response at different timepoints. **Tumor shrinkage of target lesions; 1 Patient A - DL5 - 23 is off study at data cut - off; 2 Patient out of study due to PD (external assessment); Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with PD at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Overall survival (OS) and progression - free survival (PFS) censored at data - cut; BL: Baseline PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; DCR: Disease control rate, mFU: median follow - up 54% (14/26) cORR 12.1 months (4.2, 25.5+ months) 9.3 months median DOR (min, max) mFU 7/14 confirmed responses ongoing 6.0 months (0.3+, 26.8+ months) median PFS (min, max) Not reached (0.3+, 26.8+ months) 8.6 months median OS (min, max) mFU 62% (16/26) O R R 88% (23/26) Tumor shrinkage ** 92% (24/26) DCR (at week 6)
Response Over Time of IMA203 in Melanoma Durable Responses 2 Years+ after Treatment in Heavily Pretreated Patients in Phase 1b (N=28 # ) 8 Ongoing Scans at approximately week 6, month 3 and then every 3 months Data cut - off Aug 23, 2024 # First tumor assessment post infusion pending for two melanoma patients at data - cut; *Tumor shrinkage of target lesions; 1 Patient out of study due to PD (external assessment) 2 Patient A - DL5 - 23 is off study at data cut - off; Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with PD at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Overall survival (OS) and progression - free surviv al (PFS) censored at data - cut; BL: Baseline PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; DCR: Disease control rate, mFU: median follow - up 54% (14/26) cORR 12.1 months (4.2, 25.5+ months) 9.3 months median DOR (min, max) mFU 7/14 confirmed responses ongoing 6.0 months (0.3+, 26.8+ months) median PFS (min, max) Not reached (0.3+, 26.8+ months) 8.6 months median OS (min, max) mFU 62% (16/26) O R R 88% (23/26) Tumor shrinkage ** 92% (24/26) DCR (at week 6)
Significant Shift in PFS and OS Between Dose Escalation & Dose Expansion PFS of 6 Months and OS Not Reached in Melanoma Efficacy Population 9 Progression Free Survival Data cut - off Aug 23, 2024 Overall Survival Overall survival (OS) and progression - free survival (PFS) censored at data - cut; * These data are derived from different clinical trials at different points in time with differences in trial design and patient populations. As a result, cross - trial comparisons cannot be made, and no head - to - head clinical trials have been conducted. mPFS N 2.6 months 11 Dose Escalation 6.0 months 28 Dose Expansion mOS N 6.3 months 11 Dose Escalation Not reached 28 Dose Expansion Log - rank test: p=<0.0001 Log - rank test: p=0.0003 • Significant shift in PFS and OS between melanoma patients treated during the dose escalation and dose expansion phase • PFS in dose escalation is comparable to reported data in 2L+ cut. melanoma population* • OS in dose escalation is shorter than reported OS for 2L+ cut. melanoma population* • All patients in the dose escalation group died and 20/26 patients are alive in dose expansion
IMA203 Phase 1b in Melanoma: Overview of Studies PFS and OS Data in 2L+ Melanoma Cohorts mOS (months) mPFS (months) Prior lines of therapies 2L+ melanoma patient population N Phase Drug Product not reached 6.0 4% n=0, 18% n=1, 32% n=2, 29% n=3:, 4% n=4, 11% n=5, 4% n=6 86% received prior CPI (median of 1 prior line of CPI in overall population, median of 2 prior lines of CPI in cut. melanoma) Median of 2 prior lines, median of 2 prior lines in cut. melanoma 46% cutaneous 43% uveal 11% other 28 1b (Dose Expansion) IMA203 in Melanoma 6.3 2.6 0% n=1, 27% n=2, 73% n>2 prior lines 100% received prior CPI (median of 2 prior lines of CPI, median of 2.5 prior lines of CPI in cut. melanoma) Median of 4 prior lines, median of 4.5 prior lines in cut. melanoma 73% cutaneous 18% uveal 9% other 11 1a (Dose Escalation) IMA203 in Melanoma 5.3 2.5 0% n=1, 16% n=2, 84% n>2 prior lines 100% received prior CPI (median 3 prior lines of CPI) Median of 4 prior lines, median of 4.5 prior lines in cut. melanoma 63% cutaneous 11% uveal 26% other 19 1a (Dose Escalation) IMA201/202/203 combined in Melanoma 13.9 4.1 median of 3 prior lines (min/max: 1/9) 100% received prior CPI 54% cutaneous 0% uveal 45% other 153 2 Lifileucel (C - 144 - 01, Cohort 2+4) 1 11.6 2.9 57% n=1, 27% n=2, 12% n>2 prior lines 99% received prior CPI 85% cutaneous 0% uveal 15% other 238 3 Tilsotolimod + Ipilimumab (ILLUMINATE - 301) 2 14.7 2.1 46% n=1, 35% n=2, 19% n≥3 prior lines 99% received prior CPI 68% cutaneous 0% uveal 32% other 354 1/2 Nivolumab + Relatlimab (RELATIVITY - 020, D1 Cohort) 3 Data cut - off Aug 23, 2024 10 1 Chesney et al., 2022; 2 Diab et al., 2024; 3 Ascierto et al., 2023. These data are derived from different clinical trials at different points in time with differences in trial design and patient populations. As a result, cross - trial comparisons cannot be made, and no head - to - head clinical trials have been conducted.
Enhanced PFS in Phase 1b Melanoma Patients with Deep Responses N=26 # 11 • Approx. half of all patients have a deep response (>50% tumor reduction) • This subgroup of patients has highly medically meaningful mPFS of more than 1 year • Patients with <50% tumor reduction (including tumor size increase) still observe a more than 2x longer mPFS as compared to patients treated in dose escalation with suboptimal doses Data cut - off Aug 23, 2024 mPFS N 2.6 months 11 Dose Escalation IMA203 5.7 months 14* Dose Expansion IMA203 <50% tumor size reduction (including tumor size increase) 13.4 months 12 Dose Expansion IMA203 > 50% tumor size reduction # Excluding two patients that were infused but did not have their first tumor assessment post baseline at data - cut; *Includes one patient with ongoing SD 4.4 months after infusion with tumor reduction <50% Log - rank: p=0.0033
0 5 î 10 5 1 î 10 6 1.5 î 10 6 2 î 10 6 2.5 î 10 6 Cmax (vector copies/μg gDNA) 4 6 8 10 Infused Total (CD8 + Dex + ) IMA203 T cell dose (x10 9 ) 2 1 0 Dose Response Relationship IMA203 T Cell Dose is Associated with Clinical Activity and IMA203 T Cell Exposure (N=65 out of 68*) 12 RP2D cPR (n=23) PR or SD or PD (n=42) IMA203 T Cell Dose is Associated with Clinical Activity IMA203 T Cell Dose Correlates with T Cell Exposure 1 Mann - Whitney U test, 2 Spearman Correlation; * no data available yet for patients recently treated; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; , RP2D: recommended phase 2 dose p = 0.0180 1 r=0.8396 p=1.646e - 018 2 Data cut - off Aug 23, 2024
Exposure Response Relationship IMA203 T Cell Persistence Over Time and T Cell Exposure is Associated with Clinical Response 13 Rapid T cell engraftment (C max ) in all patients with over two years of persistence Higher C max and persistence in patients treated at higher doses in dose expansion versus dose escalation cPR P R / S D / P D 1 Mann - Whitney U test; * no data available yet for patients recently treated; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response, AUC: Area under curve Data cut - off Aug 23, 2024 1 1 î 10 2 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 1 î 10 7 2 8 1 4 2 0 2 6 2 8 4 8 6 8 8 8 200 400 600 800 Persistence Overtime Days post infusion Vector copies/ ug gDNA N = 2 7 N = 3 8 Persistence over Time Dose Escalation Dose Expansion N=65 out of 68* N=65 out of 68* IMA203 T cell exposure (C max & AUC (0 - 28d) ) is associated with clinical responses 1 î 10 7 2 î 10 7 3 î 10 7 AUC (0 - 28d) of TCR T Cell Concentration in Blood (vector copies/μg DNA) p = 0.0517 1 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 1 î 10 7 2 8 1 4 2 0 2 6 2 8 4 8 6 8 8 8 200 400 600 800 Days post infusion Vector copies/ ug gDNA
Patient Case A - DL4 - 03 : Cutaneous Melanoma 14 Images courtesy of treating physician (Dr. Martin Wermke, University of Dresden) PET - based Complete Response 15 Months Post Infusion and Ongoing Response at 24 Months 51 - year - old male patient with complete remission according to PET imaging after 15 months and ongoing beyond two years post infusion at data cut • 5 prior systemic treatment lines: • Dabrafenib + Trametinib • Pembrolizumab • Dabrafenib + Trametinib + Vemurafenib + Cobimetinib • Tebentafusp • Encorafenib + Binimetinib • 13 years of cancer history • 23 mm target lesion in cervical lymph node and non - target lesions in pelvic bone and lung • Patient received ~1.3x10 9 IMA203 TCR - T cells • Ongoing PR at 24 months post infusion with - 78.3% reduction according to RECIST1.1 • Metabolic complete response reported based on investigator - initiated PET imaging at baseline and month 15 post infusion Follow - up Month 15 Follow - up Month 27 (Post data cut - off) Baseline Follow - up Month 12 Data cut - off Aug 23, 2024
SUPRAME: Registration - enabling Randomized Phase 3 Trial Trial Design Following Recent Type D Meeting with FDA and SA Meeting with PEI 1 15 ACTengine® IMA203 N=180 Investigator’s choice of selected approved treatments N=1 8 0 Endpoints • Primary Endpoint • PFS • Secondary Endpoints • Safety • ORR + DOR • No OS detriment • Patient - reported outcomes (EORTC QLQ - C30, EQ - 5D - 5L) mPFS: median progression - free survival, ORR: objective response rate; 1 Scientific Advice Meeting with Paul - Ehrlich - Institute, the German regulatory authority Randomization 1 : 1 Next Steps • SUPRAME Phase 3 trial is projected to commence in December 2024 • Pre - specified interim analysis planned after approx. 200 patients enrolled • Full enrollment anticipated by late 2026 Patient Population: unresectable or metastatic melanoma post - treatment with a checkpoint inhibitor (2L+) N=360
ACTengine® IMA203 TCR - T Monotherapy Targeting PRAME in Melanoma Summary of Clinical Data Tolerability PFS & OS Biological Data Broad Reach Favorable tolerability profile: mostly mild to moderate CRS; infrequent ICANS (5.7% Gr1, 4.3% Gr2, 4.3% Gr3); no treatment related deaths Anti - Tumor Activity & Durability 54% (14/26) cORR and 92% (24/26) DCR; 12.1 months mDOR and ongoing responses for over two years PFS of 6 months and OS not reached (mFU 8.6 months) T cell dose and exposure are significantly associated with clinical response FDA RMAT designation received in multiple PRAME expressing cancers including cutaneous and uveal melanoma Data cut - off Aug 23, 2024 16 SUPRAME Phase 3 trial is projected to commence in December 2024
17 We are Immensely Grateful to the Patients, Their Families … University Hospital Dresden University Hospital Bonn University Hospital Würzburg University Hospital Hamburg Ge r ma n y Dr. M. Wermke Charité Berlin University Hospital Heidelberg University Medicine Mainz Columbia U n iv e rsity University of Pittsburgh MD Anderson Cancer Center United States University of Miami Health System Fox Chase Cancer Center … and the Investigators at the Clinical Sites Sponsor: Immatics
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Tolerability Profile of IMA203 Across All Dose Levels in Phase 1a/b All ≥Grade 3 Adverse Events (N=70 1 ) TEAEs by maximum severity for all patients in Phase 1a and Phase 1b (N=70 1 ) Data cut - off Aug 23, 2024 19 ≥ Grade 3 Adverse event ( System organ class , Preferred term) % No. 100.0 70 Patients with any adverse event 12.9 9 Adverse Events of Special Interest 11.4 8 Cytokine release syndrome 4.3 3 ICANS 2 100.0 70 Blood and lymphatic system disorders 88.6 62 Neutropenia 55.7 39 Lymphopenia 54.3 38 Leukopenia 51.4 36 Anaemia 34.3 24 Thrombocytopenia 2.9 2 Febrile neutropenia 1.4 1 Cytopenia 1.4 1 Leukocytosis 14.3 10 Infections and infestations 2.9 2 Urinary tract infection 1.4 1 Appendicitis 1.4 1 COVID - 19 1.4 1 Cytomegalovirus infection reactivation 1.4 1 Enterococcal infection 1.4 1 Human herpesvirus 6 encephalitis 1.4 1 Infection 1.4 1 Orchitis 1.4 1 Sepsis 3,4 1.4 1 Septic shock 3 14.3 10 Investigations 8.6 6 Alanine aminotransferase increased 7.1 5 Aspartate aminotransferase increased 2.9 2 Blood creatinine increased 1.4 1 Blood alkaline phosphatase increased 1.4 1 Blood bilirubin increased 1.4 1 Blood fibrinogen decreased 1.4 1 Lymphocyte count increased 14.3 10 Respiratory, thoracic and mediastinal disorders 5.7 4 Hypoxia 2.9 2 Pleural effusion 1.4 1 Bronchial obstruction 1.4 1 Dyspnoea 1.4 1 Epistaxis 1.4 1 Laryngeal inflammation 1.4 1 Respiratory failure All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment . Adverse events were coded using the Medical Dictionary for Regulatory Activities . Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 5 . 0 . Grades for Cytokine release syndrome and ICANS were determined according to CARTOX criteria (Neelapu et al . , 2019 ) . Patients are counted only once per adverse event and severity classification . Based on interim data extracted from open clinical database ( 23 - Aug - 2024 ) ; 1 Two patients with disease progression after first IMA 203 infusion received exploratory second IMA 203 infusion . They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table : First patient : Abdominal pain, Cytokine release syndrome, Diarrhoea, Hypokalaemia, Proteinuria ; Second patient : Humerus fracture, Muscle spasms, Neutropenia, Thrombocytopenia ; 2 ICANS : Immune effector cell - associated neurotoxicity syndrome ; 3 Fatal Adverse events were not considered related to any study drug ; 4 Patient died from sepsis of unknown origin and did not receive IMA 203 TCR - T cells ; 5 DLT : Dose limiting toxicity in phase 1 a at DL 2 reported on March 17 , 2021 . table continued… 10.0 7 Metabolism and nutrition disorders 4.3 3 Hypokalaemia 4.3 3 Hyponatraemia 2.9 2 Hypophosphataemia 1.4 1 Dehydration 1.4 1 Failure to thrive 10.0 7 Vascular disorders 8.6 6 Hypertension 1.4 1 Hypotension 8.6 6 Renal and urinary disorders 5.7 4 Acute kidney injury 1.4 1 Nephritis 1.4 1 Proteinuria 7.1 5 Gastrointestinal disorders 4.3 3 Abdominal pain 1.4 1 Diarrhoea 1.4 1 Ileus 1.4 1 Vomiting 5.7 4 General disorders and administration site conditions 1.4 1 Fatigue 1.4 1 General physical health deterioration 3 1.4 1 Pyrexia 1.4 1 Swelling face 5.7 4 Skin and subcutaneous tissue disorders 4.3 3 Rash maculo - papular 1.4 1 Eczema 4.3 3 Cardiac disorders 4.3 3 Atrial fibrillation 5 2.9 2 Eye disorders 1.4 1 Periorbital oedema 1.4 1 Ulcerative keratitis 2.9 2 Injury, poisoning and procedural complications 1.4 1 Humerus fracture 1.4 1 Infusion related reaction 2.9 2 Musculoskeletal and connective tissue disorders 1.4 1 Back pain 1.4 1 Muscle spasms Adverse event ( System organ class , Preferred term) ≥ Grade 3 No. % table continued… 2.9 2 Nervous system disorders 1.4 1 Headache 1.4 1 Posterior reversible encephalopathy syndrome 1.4 1 Endocrine disorders 1.4 1 Inappropriate antidiuretic hormone secretion 1.4 1 Hepatobiliary disorders 1.4 1 Cholangitis 1.4 1 Immune system disorders 1.4 1 Haemophagocytic lymphohistiocytosis 1.4 1 Reproductive system and breast disorders 1.4 1 Vaginal haemorrhage Adverse event ( System organ class , Preferred term) ≥ Grade 3 No. %
IMA203 Phase 1 Patient Population Flow Chart 20 Data cut - off Aug 23, 2024 * Melanoma efficacy population excludes 5 patients treated at DL4 in Phase 1a of the trial as reported in the May 2024 update, based on different manufacturing version used that affects the T cell product (see slide 22); Current manufacturing version: T cell enrichment process using monocyte depletion (negative selection) or CD8/CD4 positive selection; prior manufacturing version: manufacturing process without specific T cell enrichment; 1 Except one DL3 patient with current manufacturing version. Total Safety Population (N=70 enrolled patients) N=1 patient in Phase 1a started lymphodepletion but did not receive IMA203 N=1 patient had lymphodepletion but IMA203 infusion was scheduled after data cut - off N=68 patients treated with IMA203 N=27 patients in Phase 1a Dose Escalation (DL1 - 4) N=11 melanoma patients N=16 non - melanoma patients N=41 patients in Phase 1b Dose Expansion (DL4/5, RP2D) Melanoma Efficacy Population * (n=28) thereof 2 patients without post - baseline scan N=13 non - melanoma patients N=6 melanoma patients (DL1 - 3) N=5 melanoma patients (DL4) Previous manufacturing version Previous manufacturing version 1 Current manufacturing version Current manufacturing version Thereof n=65 evaluable for T cell exposure analysis Thereof n=38 evaluable for T cell persistence analysis
Baseline Characteristics of Melanoma Patients in Phase 1a and Phase 1b Focus on Cutaneous and Uveal Melanoma Melanoma Efficacy Population 1 Melanoma Dose Escalation Population Uveal Melanoma (N=12) Cutaneous Melanoma (N=13) Uveal Melanoma (N=2) Cutaneous Melanoma (N=8) Indication 2.5 (0, 6) 1 (0, 4) 2 (1, 5) 2 (1, 3) 2 (2, 2) 1 (1,1) 4.5 (2, 7) 2.5 (2,4) Prior lines of systemic treatment (median, min, max) Thereof CPI (melanoma only) (median, min, max) 58.3 69.2 100.0 75.0 LDH at baseline >1 x ULN [% of patients] 107.5 (38.6, 210.0) 123.0 (15.0, 309.8) 153,5 (109.9, 198.0) 106.3 (37.0, 211.0) Baseline tumor burden Median Target lesion sum of diameter [mm] (min, max) 91.7 69.2 100.0 50.0 Liver/brain lesions at baseline [% of patients] DL4/DL5 DL4/DL5 EC1, DL3 EC1/DL4 Dose level 4.33 (1.62, 8.43) 4.04 (1.3, 10.2) 0.417 (0.248, 0.586) 1.115 (0.099, 2.09) Total infused dose TCR - T cells [x10 9 ] Data cut - off Aug 23, 2024 21 1 All infused melanoma patients in Ph1b dose expansion; CPI: Checkpoint inhibitors; EC1: 0.06 - 0.12x10 9 TCR - T cells/m 2 BSA; DL3: 0.2 - 0.48x10 9 TCR - T cells/m 2 BSA ; DL4: 0.2 - 1.2x10 9 TCR - T cells/m 2 BSA, DL5: 1.201 - 4.7x10 9 TCR - T cells/m 2 BSA Cutaneous melanoma patients in Phase 1b had similar prior CPI exposure, higher tumor burden and higher incidence of liver/brain lesions compared to Phase 1a
Favorable TCR - T Product Characteristics and High TCR - T Levels in Patients Manufacturing Improvements Implemented in Phase 1b Enhance Key Features of the Cell Product 22 Robust TCR - T product features Increased peak IMA203 T cell levels in patients DL4 only, normalized to cell dose Data cut - off Aug 23, 2023 1 Current: T cell enrichment process using monocyte depletion (negative selection) or CD8/CD4 positive selection; prior: manufacturing process without specific T cell enrichment; 2 one patient started lymphodepletion but did not receive IMA203 T cells; 3 no data available yet for patients recently treated * • Manufacturing improvements including T cell enrichment process (i.e. removal of monocyte fraction or CD8/CD8 selection) implemented in Phase 1b lead to improved TCR - T product features and increased TCR - T levels in patients • The efficacy - evaluable population in this analysis (data cut - off Aug 23, 2024) focuses on this patient population only and reflects the expected population and product to be evaluated in the pivotal trial 0 2 0 4 0 6 0 8 0 100 %TCR+ (of CD3+CD8+ cells) P < 0.0001 0 5 î 10 9 1 î 10 10 1.5 î 10 10 2 î 10 10 Total TCR+ T Cells P < 0.0001 GEN1 prior (n=27) I M A 203 I M A 203 GEN1 cu rr ent (n=43) 0 2 î 10 5 4 î 10 5 6 î 10 5 8 î 10 5 Vector copies/μg gDNA P = 0.0003 GEN 1 p r ior (n=7) IMA203 IMA203 GEN1 cu rr ent (n=9) Man u f actur i ng proces s 1 2 3
T Cell Selection Results in ‘Younger’ Phenotype of the TCR - T Product Consequently, Terminally Differentiated T Cells are also Decreased 23 L = Low enrichment (n=7, prior manufacturing version) M = Medium enrichment (n=37, current manufacturing version) H = High enrichment (n=38, current manufacturing version) Presented at the Process Development Summit 2024; L: No specific T cell enrichment; M: monocyte depletion (negative selection); H: CD4/CD8 T cell selection (positive selection); Results are represented as separated scatter with median; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, ns = not significant by a two - way ANOVA with Tukey’s Multiple Comparisons. L M H L M H L M H L M H 0 4 0 2 0 6 0 8 0 1 0 0 %Positive (Gated off CD8+ ) T na i ve T - cm T - em T - eff n s ٓٓ ٓٓٓٓ n s n s n s n s ٓٓٓٓ ٓٓٓٓ n s n s n s
Melanoma Patients Treated with IMA203 in Phase 1b Dose Expansion Efficacy - evaluable Population (n=28*) Reason for Progression Comment BOR (Max % change of target lesions) B OR Total infused dose TCR - T cells 1 [x10 9 ] Prior treatments No of prior treatment lines Indication Patient ID Ongoing response at 26.8 months PFS - 83.9 cPR 4.16 ARRY614 + Nivolumab 1 Uveal Melanoma A - DL5 - 01 Ongoing response at 26.5 months PFS - 78.3 cPR 1.30 Dabrafenib + Trametinib Pembrolizumab Dabrafenib + Trametinib + Vemurafenib + Cobimetinib T eben taf us p Encorafenib + Binimetinib 5 Cut. Melanoma A - DL4 - 03 Ongoing response at 12.0 months PFS - 56.3 cPR 9.80 Nivolumab Pembrolizumab Ipilimumab + Nivolumab 3 Cut. Melanoma A - DL5 - 13 Ongoing response at 8.6 months PFS - 77.9 cPR 7.19 Valproic acid + Sunitinib Tebentafusp 2 Uveal Melanoma A - DL5 - 21 Ongoing response at 7.3 months PFS - 60.4 cPR 8.14 Melphalan Tebentafusp 2 Uveal Melanoma A - DL5 - 26 Ongoing response at 7.0 months PFS - 66.7 cPR 10.20 Relatlimab + Nivolumab 1 Cut. Melanoma A - DL5 - 27 Ongoing stable disease at 4.2 months PFS - 4.1 SD 3.68 Ipilimumab + Nivolumab AB122 + AB154 Encorafenib + Binimetinib 3 Cut. Melanoma A - DL5 - 31 Ongoing response at 6 months PFS, patient off study at data - cut due to investigator decision (radiation of one target lesion) - 44.8 cPR 6.94 Ipilimumab + Nivolumab Encorafenib + Binimetinib Relatlimab + Nivolumab 3 Cut. Melanoma A - DL5 - 23 Progression as determined by external assessment Response until 13.4 months PFS - 65.1 cPR 5.12 Interferon Pembrolizumab Ipilimumab + Nivolumab 3 Cut. Melanoma A - DL5 - 03 Non - target lesion progression Response until 8.5 months PFS - 50.9 cPR 5.42 Pembrolizumab Clinical trial intrahepatic PV10 Ipilimumab + Nivolumab Clinical trial Anti - CTLA - 4 NF AB + XRT Clinical trial foghorn FHD - 286 Pembrolizumab 6 Uveal Melanoma A - DL5 - 19 Non - target lesion progression and new lesions Response until 6.2 months PFS - 4 8.1 cPR 2.89 NOX66 - 005 Idronoxil with radiotherapy IDE196 + Crizotinib LVGN3616 + LVGN6051 + LVGN7409 + Bevacizumab + Cyclophosphamide 3 Uveal Melanoma A - DL5 - 24 Target lesion and non - target lesion progression Response until 6.0 months PFS - 57.1 cPR 7.94 Nivolumab Ipilimumab + Nivolumab 2 Mucosal Melanoma A - DL5 - 29 Target lesion progression Response until 5.8 months PFS - 40.8 cPR 2.68 SEAGEN CD40 Agonist 1 Uveal Melanoma A - DL5 - 10 New lesions Response until 5.7 months PFS - 65.9 cPR 1.55 Nivolumab + Ipilimumab Brektovi + Mektovi + Nivolumab + Relatlimab 2 Cut. Melanoma A - DL4 - 07 New lesions Response until 5.6 months PFS - 58.8 cPR 3.02 Pembrolizumab 1 Cut. Melanoma A - DL5 - 15 * First tumor assessment post infusion pending for two melanoma patients at data - cut; 1 Transduced viable CD8 T cells; BOR: Best overall response; DL: Dose level; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; PFS: Progression - free survival (censored at data - cut) Data cut - off Aug 23, 2024 24
Reason for Progression Comment BOR (Max % change of target lesions) BOR Total infused dose TCR - T cells 1 [x10 9 ] Prior treatments No of prior treatment lines Indication Patient ID New lesions Disease stabilization until 2.7 months post infusion, unconfirmed response from 2.7 until 5.5 months PFS - 59.3 PR 6.31 I pili m u ma b+Ni v o l u mab Tafinlar + Mekinist 2 Cut. Melanoma A - DL5 - 22 Target lesion progression Unconfirmed response until 2.8 months PFS - 36.9 PR 3.33 Ipilimumab + Nivolumab Avapritinib Opdualag 3 Mucosal Melanoma A - DL5 - 28 Non - target lesion progression Disease stabilization until 8.6 months PFS - 17.6 SD 8.43 Ipilimumab + Pembrolizumab Tebentafusp Ipilimumab + Nivolumab IDE196 + Binimetinib FHD - 286 5 Uveal Melanoma A - DL5 - 20 New lesion Disease stabilization until 6.1 months PFS - 18.6 SD 4.04 Ipilimumab + Nivolumab+Tociliziumab Nivolumab + Relatlimab + Tocilizumab + Ipilimumab 2 Cut. Melanoma A - DL5 - 17 New lesions, target lesion progression Disease stabilization until 5.9 months PFS 11.4 SD 1.63 Nivolumab Nivolumab + Ipilimumab Dabrafenib + Trametinib Nivolumab 4 Cut. Melanoma A - DL4 - 05 Non - target lesion progression and a new lesion Disease stabilization until 5.7 months PFS 0.0 SD 1.73 Ipilimumab + Nivolumab 1 Melanoma (Unk. Primary) A - DL4 - 04 New lesion Disease stabilization until 5.5 months PFS - 25.4 SD 5.71 Tebentafusp Ipilimumab + Nivolumab 2 Uveal Melanoma A - DL5 - 18 Target and non - target lesion progression, new lesions Disease stabilization until 3.5 months PFS - 22.6 SD 4.50 Tyrosinase peptides Nivolumab + Ipilimumab + Denosumab Tebentafusp 3 Uveal Melanoma A - DL5 - 12 Non - target lesion progression, new lesions Disease stabilization until 2.7 months PFS 4.6 SD 5.14 Ipilimumab + Nivolumab Axitinib + Nivolumab 2 Cut. Melanoma A - DL5 - 25 New lesion Progressive disease at 1.4 months PFS - 6.3 PD 2.56 NA 0 Uveal Melanoma A - DL4 - 06 New lesions Progressive disease at 1.4 months PFS - 41.5 PD 2.34 Nivolumab Encorafenib + Binimetinib 2 Cut. Melanoma A - DL5 - 14 First scan post infusion pending at data cut - off N/A N/A 3.18 Ipilimumab + Nivolumab Tebentafusp Ipilimumab + Nivolumab DYP - 688 Ipilimumab + Nivolumab 5 Uveal Melanoma A - DL5 - 32 First scan post infusion pending at data cut - off N/A N/A 1.62 Ipilimumab + Nivolumab Darovasertib Tebentafusp 3 Uveal Melanoma AA - 1 Data cut - off Aug 23, 2024 25 Melanoma Patients Treated with IMA203 in Phase 1b Dose Expansion (cont.) Efficacy - evaluable Population (n=28*) *First tumor assessment post infusion pending for two melanoma patients at data - cut; 1 Transduced viable CD8 T cells; BOR: Best overall response; DL: Dose level; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; PFS: Progression - free survival (censored at data - cut)
Patient Case A - DL5 - 01: Uveal Melanoma Long - term Responder Ongoing at 26+ Months B a seline Follow - up Month 1 - 51% PR Follow - up Month 26 - 83% PR 71 - year - old male patient with ongoing shrinkage of liver lesion 26+ months post treatment • 1 prior line of systemic treatment: ARRY614 + Nivolumab • 6 years of cancer history • 99.2 mm target lesion sum • Patient received ~4x10 9 IMA203 TCR - T cells RECIST Change from Baseline (%) Overall RECIST1.1 assessment CT scans courtesy of treating physician (Dr. Jason Luke, University of Pittsburgh) Data cut - off Aug 23, 2024
Patient Case A - DL5 - 033: Cutaneous Melanoma Changes of a Melanoma Lesion of the Skin within 8 Days (Post Data Cut - off) Data cut Aug 23, 2024; Patient was treated post data cut - off date (Aug 26, 2024); Images courtesy of treating physician (Dr. Jason Luke, University of Pittsburgh) Follow - up Day 15 Follow - up Day 8 Base l i n e 61 - year - old male patient demonstrated changes of a melanoma lesion of the skin 8 days post IMA203 infusion • 4 prior systemic treatment lines: 3 lines of CPI, 1 line of Brenetafusp (PRAME) • 8 years of cancer history • 118 mm target lesion sum • Patient received ~10x10 9 IMA203 TCR - T cells
Deli v ering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. www.immatics.com
Exhibit 99.3
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation October 10, 2024
Forward - Looking Statement This presentation (“Presentation”) is provided by Immatics N . V . (“Immatics” or the “Company”) for informational purposes only . The information contained herein does not purport to be all - inclusive and none of Immatics, any of its affiliates, any of its or their respective control persons, officers, directors, employees or representatives makes any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation . Forward - Looking Statements . Certain statements in this presentation may be considered forward - looking statements . Forward - looking statements generally relate to future events or the Company’s future financial or operating performance . For example, statements concerning timing of data read - outs for product candidates, the timing, outcome and design of clinical trials, the nature of clinical trials (including whether such clinical trials will be registration - enabling), the timing of IND or CTA filing for pre - clinical stage product candidates, the timing of BLA filings for clinical stage product candidates, estimated market opportunities of product candidates, manufacturing timetables, capacity and success rates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward - looking statements . In some cases, you can identify forward - looking statements by terminology such as “may”, “should”, “expect”, “plan”, “target”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology . Such forward - looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements . These forward - looking statements are based upon estimates and assumptions that, while considered reasonable by Immatics and its management, are inherently uncertain . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual Report on Form 20 - F and other filings with the Securities and Exchange Commission (SEC) . Nothing in this presentation should be regarded as a representation by any person that the forward - looking statements set forth herein will be achieved or that any of the contemplated results of such forward - looking statements will be achieved . You should not place undue reliance on forward - looking statements, which speak only as of the date they are made . The Company undertakes no duty to update these forward - looking statements . No Offer or Solicitation . This communication is for informational purposes only and does not constitute, or form a part of, an offer to sell or the solicitation of an offer to sell or an offer to buy or the solicitation of an offer to buy any securities, and there shall be no sale of securities, in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction . No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933 , as amended, or in an offering exempt from registration . Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company’s own internal estimates and research . In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions . Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source . All the scientific and clinical data presented within this presentation are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification . 2
Therapeutic Op p o rt u n ity Potential for addressing large patient populations with high prevalence targets in solid tumors Two Clinical - Stage Modalities Pipeline of TCR - T and TCR Bispecific product candidates in clinical & preclinical development Building a Leading TCR Therapeutics Company 3 I n t r o D i f f e r e n ti a t ed Platforms Unique technologies to identify true cancer targets and right TCRs Clinical PoC for Cell Therapy High confirmed objective response rate and durable responses in melanoma; registration - enabling Phase 3 trial to commence in December 2024
2H2024 Catalysts for ACTengine® and TCER® Clinical Lead Assets Projected Cash Runway into 2027 to Reach Multiple Value Inflections Points 4 • Targeted randomized Phase 3 trial 1 for ACTengine® IMA203 in 2L+ melanoma in 2024 • Clinical data update from Phase 1b dose expansion trial at SMR Conference on Oct 11, 2024; next IMA203CD8 (GEN2) update at SITC Conference on Nov 9, 2024 ACTengine® IMA203 / IMA203CD8 (PRAME) First clinical data update from dose escalation in ongoing Phase 1 trial at ESMO on Sep 16, 2024 TCER® IMA401 (MAGEA4/8) First clinical data update from dose escalation in ongoing Phase 1/2 trial planned in 4Q 2024 with initial focus on early doses and melanoma Planned focus indications: melanoma, ovarian cancer, uterine cancer, lung cancer, and others TCER® IMA402 (PRAME) Updates planned across the entire clinical portfolio throughout 2024 I n t r o
Two Distinct TCR - based Therapeutic Modalities in Clinical Development 5 Differentiated positioning of ACTengine® vs. TCER® based on patient population and medical need I n t r o 1 Interim data update from the ACTengine® IMA203 (published Oct 10, 2024) and IMA203CD8 monotherapies (published November 08, 2023) TCR Bispecifics (TCER®) Autologous TCR - T (ACTengine®) • Strong clinical activity in patients with high tumor burden 1 • Single dose • Proprietary manufacturing process for enhanced potency of T cells • Specialized medical centers • Target requirements: stringent tumor selectivity, low, medium, high copy numbers • Off - the - shelf biologic for immediate treatment • Repeat dosing • All hospitals and out - patient, opportunity for larger patient reach • Favorable commercial characteristics • Target requirements: strong tumor association, medium to high copy numbers
Our Pipeline of TCR - based Adoptive Cell Therapies and Bispecifics 6 I n t r o 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion; 2 Immatics’ proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing technology; 3 mRNA - enabled in vivo expressed TCER® molecules Phase 3 Phase 2 Phase 1b 1 Phase 1a 1 Preclinical Target Product Candidate Modality PRAME ACTengine® IMA203 Autologous ACT PRAME ACTengine® IMA203CD8 COL6A3 ACTengine® IMA204 Undisclosed Multiple programs Undisclosed 2 ACTallo® IMA30x Allogeneic ACT γδ T cells Undisclosed Multiple programs MAGEA4/8 TCER® IMA401 Bispecifics PRAME TCER® IMA402 Undisclosed TCER® IMA40x Undisclosed Multiple programs 3
Realizing the Full Multi - Cancer Opportunity of PRAME ACTengine® IMA203 (TCR - T) and TCER® IMA402 (TCR Bispecific) 7 A C T en g i ne® IMA203 (TCR - T) Cancer Cell Death PRAME is one of the most promising and most prevalent, clinically validated solid tumor targets known to date Leverage the full potential of targeting PRAME by continued evaluation of the best suited therapeutic modality (ACTengine® vs. TCER® or both) for each cancer type I n t r o Phase 1b dose expansion ongoing Phase 3 trial in preparation TCER® IMA402 (TCR Bispecific) 1 PRAME target prevalence is based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; 2 Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=61); NSCLC: Non - small cell lung cancer, TNBC: Triple - negative breast cancer, HNSCC: Head and neck squamous cell carcinoma; HCC: Hepatocellular carcinoma % PRAME positive patients 1 Indication 97% 100% up to 100% 95% 89% 84% 68% 63% 45% up to 40% 33% 27% 27% 26% 25% 18% 18% Uterine Carcinoma Uterine Carcinosarcoma Sarcoma Subtypes Cut. Melanoma Uveal Melanoma 2 Ovarian Carcinoma Squamous NSCLC T N B C Small Cell Lung Cancer Kidney Carcinoma C h ol angio c a r c i n o ma H NSCC Esophageal Carcinoma Breast Carcinoma Adeno NSCLC HCC Bladder Carcinoma Dose escalation of Phase 1/2 trial ongoing
ACTengine® IMA203 – TCR - T Targeting PRAME 8
The Multi - Cancer Opportunity of PRAME One of the Most Promising Solid Tumor Targets for TCR - based Therapies Known To Date 9 High prevalence High target density Homogeneous expression “Clean” expression profile Clinical proof - of - concept s qNSC L C Ovarian Cancer PRAME fulfills all properties of an ideal target for TCR - based therapies PRAME RNA detection in tumor samples (ISH) ISH: in situ hybridization, sqNSCLC: squamous non - small cell lung cancer I MA2 0 3
Patient Population PRAME Positive R/R Incidence Incidence Selected Indications Based on R/R Incidence; PRAME and HLA - A*02:01+ 2,999 95% 7,700 99,800 Cut. Melanoma 292 89% 800 1,500 Uveal Melanoma 4,408 84% 12,800 19,900 Ovarian Carcinoma 4,255 97% 10,700 62,700 Uterine Carcinoma 779 100% 1,900 3,300 Uterine Carcinosarcoma 9,646 68% 34,600 57,000 Squamous NSCLC 3,579 45% 19,400 31,900 Small Cell Lung Cancer 5,668 25% 55,300 91,200 Adeno NSCLC 1,672 27% 15,100 66,500 HNSCC 4,669 TNBC: 63% 26% 43,800 290,600 Breast Carcinoma 164 100% 400 1,000 Synovial Sarcoma 947 33% 7,000 8,000 C ho l a n g io c a r c i noma IMA203 TCR - T Has the Potential to Reach a Large Patient Population ~39,000 Patients per Year in the US only 10 Incidences based on public estimates and Immatics internal model; Relapsed/refractory (R/R) or last - line patient population approximated by annual mortality; Estimated 41% HLA - A*02:01 positive population in the US; PRAME target prevalence is based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=61) Multiple opportunities to broaden patient reach and patient benefit: » Expand beyond US population » Expand into other indications such as kidney, esophageal, bladder, other liver cancers, other sarcoma subtypes through indication - specific or indication - agonistic label expansion » Move into earlier lines of therapy (R/R Incidence Incidence) » Inclusion of patients with lower PRAME - threshold TOTAL ~39,000 annually in the US I MA2 0 3
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ a ing - T Approach 11 I MA2 0 3 LEUKAPHARESIS
ACTengine® IMA203 TCR - T Product Manufacturing Differentiated Manufacturing Process and Setup 1 - week manufacturing process followed by 1 - week QC release testing High manufacturing success rate of >95% to reach IMA203 targ t os Lean and cost - efficient process Proprietary Manufacturing Process 12 I MA2 0 3 SHO R T SIMPLE R OBU S T *IMA203: RP2D 1 - 10x10 9 total TCR - T cells Manufacturing of ACTengine® candidates & other future autologous /allogeneic candidates Early - stage and registration - directed clinical trials as well as initial commercial supply ~100,000 sq ft in Houston area, TX – modular design for efficient and cost - effective scalability Construction completed in 2024 State - of - the - art Research & GMP Manufacturing Facility
ACTengine® IMA203 TCR - T Monotherapy – Patient Flow HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase Manufacturing by Immatics Infusion of ACTengine® IMA203 TCR - T Product Lymphodepletion * Low dose IL - 2 ** Safety and efficacy monitoring for 12 months Leukapheresis x x Expression Antigen 1 2 3 * 30 mg/m 2 Fludarabine and 500 mg/m 2 Cyclophosphamide for 4 days; ** 1m IU daily days 1 - 5 and twice daily days 6 - 10 Short process time of 14 days 7 - day manufacturing process applying CD8/CD4 T cell selection 7 - day QC release testing 95% (138/146) Cut. Melanoma 89% (54/61) Uveal Melanoma 93% (14/15) Uterine Carcinoma 81% (48/59) Ovarian Carcinoma Target Profiling IMADetect® mRNA assay using Immatics’ MS - guided threshold; Biopsy or archived tissue Patient screening data from Immatics’ clinical trials Data cut - off Aug 23, 2024 13 I MA2 0 3
ACTengine® IMA203 TCR - T Trial in Melanoma Heavily Pretreated Patient Population Data cut - off Aug 23, 2024 14 1 See patient flow in appendix. 2 All infused patients; *Cutaneous melanoma patients had a median of 2 prior lines of checkpoints, see appendix; RP2D: recommended phase 2 dose; CPI: Checkpoint inhibitors; EC1: 0.06 - 0.12x10 9 TCR - T cells/m 2 BSA; DL3: 0.2 - 0.48x10 9 TCR - T cells/m 2 BSA, DL4: 0.2 - 1.2x10 9 TCR - T cells/m 2 BSA, DL5: 1.201 - 4.7x10 9 TCR - T cells/m 2 BSA Melanoma Efficacy Population 2 Melanoma Dose Escalation Population Total Safety P o p ul a t i o n 1 Melanoma (Phase 1b, at RP2D) Mela n o m a (Phase 1a) All Comers (Phase 1a and Phase 1b) N= 2 8 N= 13 N= 12 N= 1 N=2 Total Cutaneous melanoma Uveal melanoma Melanoma of unknown primary Mucosal melanoma N= 1 1 N=8 N=2 N=1 Total Cutaneous melanoma Uveal melanoma Mucosal melanoma N = 7 0 N= 41 N= 29 Total M el an om a Other Number of patients 2 (0, 6) 1* (0, 4) 4 (2, 7) 2 (1, 4) 3 (0, 9) 2 (0, 4) Prior lines of systemic treatment (median, min, max) Thereof CPI (melanoma only) (median, min, max) 60 .7 81 .8 64.3 LDH at baseline >1 x ULN [% of patients] 107.5 (15.0, 309.8) 117.5 (37.0, 211.0) 117.8 (15.0, 309.8) Baseline tumor burden Median Target lesion sum of diameter [mm] (min, max) 82 .1 63 .6 65.7 Liver/brain lesions at baseline [% of patients] DL4/5 EC1/DL3/4 DL1 - 5 Dose level 4.1 (1.3, 10.2) 0.586 (0.10, 2.09) 2.09 (0.08, 10.2) Total infused dose TCR - T cells [x10 9 ] Melanoma Efficacy Population 2 (N=28) Melanoma Patients in Phase 1b Dose Expansion RP2D defined at 1 - 10x10 9 TCR - T cells (DL4/5) Total Safety Population 1 (N=70) Phase 1a Dose Escalation Dose Level 1 - 4 (total safety pop. N=28) Phase 1b Dose Expansion Dose Level 4/5 (total safety pop. N=42) I MA2 0 3
15 Data cut - off Aug 23, 2024 • Most frequent adverse events were expected cytopenias (Grade 1 - 4) associated with lymphodepletion in all patients • Mostly mild to moderate cytokine release syndrome (CRS) • 37% (26/70) Grade 1 • 46% (32/70) Grade 2 • 11% (8/70) Grade 3 2 • Infrequent ICANS (6% Grade 1, 4% Grade 2, 4% Grade 3) • No IMA203 - related deaths • Full IMA203 monotherapy tolerability profile is available in appendix • Tolerability in the melanoma subset is generally consistent with the full IMA203 monotherapy tolerability profile 1 See patient flow in appendix; 2 One grade 3 CRS only after exploratory second infusion; CRS and ICANS graded by CARTOX criteria (Neelapu et al ., 2019); ICANS: Immune Effector Cell - Associated Neurotoxicity Syndrome. Most Frequent Adverse Events of IMA203 Across All Dose Levels in Phase 1a/b N=70 Patients in Total Safety Population 1 Favorable tolerability profile for IMA203 monotherapy at recommended phase 2 dose (1x10 9 to 10x10 9 TCR - T cells) I MA2 0 3
Tolerability Profile of IMA203 Across All Dose Levels in Phase 1a/b ll ≥Gra 3 v rs v nts (N=70 1 ) TEAEs by maximum severity for all patients in Phase 1a and Phase 1b (N=70 1 ) Data cut - off Aug 23, 2024 16 ≥ Gra 3 Adverse event ( System organ class , Preferred term) % No. 100.0 70 Patients with any adverse event 12.9 9 Adverse Events of Special Interest 11.4 8 Cytokine release syndrome 4.3 3 ICANS 2 100.0 70 Blood and lymphatic system disorders 88.6 62 Neutropenia 55.7 39 Lymphopenia 54.3 38 Leukopenia 51.4 36 Anaemia 34.3 24 Thrombocytopenia 2.9 2 Febrile neutropenia 1.4 1 Cytopenia 1.4 1 Leukocytosis 14.3 10 Infections and infestations 2.9 2 Urinary tract infection 1.4 1 Appendicitis 1.4 1 COVID - 19 1.4 1 Cytomegalovirus infection reactivation 1.4 1 Enterococcal infection 1.4 1 Human herpesvirus 6 encephalitis 1.4 1 Infection 1.4 1 Orchitis 1.4 1 Sepsis 3,4 1.4 1 Septic shock 3 14.3 10 Investigations 8.6 6 Alanine aminotransferase increased 7.1 5 Aspartate aminotransferase increased 2.9 2 Blood creatinine increased 1.4 1 Blood alkaline phosphatase increased 1.4 1 Blood bilirubin increased 1.4 1 Blood fibrinogen decreased 1.4 1 Lymphocyte count increased 14.3 10 Respiratory, thoracic and mediastinal disorders 5.7 4 Hypoxia 2.9 2 Pleural effusion 1.4 1 Bronchial obstruction 1.4 1 Dyspnoea 1.4 1 Epistaxis 1.4 1 Laryngeal inflammation 1.4 1 Respiratory failure All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment . Adverse events were coded using the Medical Dictionary for Regulatory Activities . Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 5 . 0 . Grades for Cytokine release syndrome and ICANS were determined according to CARTOX criteria (Neelapu et al . , 2019 ) . Patients are counted only once per adverse event and severity classification . Based on interim data extracted from open clinical database ( 23 - Aug - 2024 ) ; 1 Two patients with disease progression after first IMA 203 infusion received exploratory second IMA 203 infusion . They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table : First patient : Abdominal pain, Cytokine release syndrome, Diarrhoea, Hypokalaemia, Proteinuria ; Second patient : Humerus fracture, Muscle spasms, Neutropenia, Thrombocytopenia ; 2 ICANS : Immune effector cell - associated neurotoxicity syndrome ; 3 Fatal Adverse events were not considered related to any study drug ; 4 Patient died from sepsis of unknown origin and did not receive IMA 203 TCR - T cells ; 5 DLT : Dose limiting toxicity in phase 1 a at DL 2 reported on March 17 , 2021 . tabl continu … 10.0 7 Metabolism and nutrition disorders 4.3 3 Hypokalaemia 4.3 3 Hyponatraemia 2.9 2 Hypophosphataemia 1.4 1 Dehydration 1.4 1 Failure to thrive 10.0 7 Vascular disorders 8.6 6 Hypertension 1.4 1 Hypotension 8.6 6 Renal and urinary disorders 5.7 4 Acute kidney injury 1.4 1 Nephritis 1.4 1 Proteinuria 7.1 5 Gastrointestinal disorders 4.3 3 Abdominal pain 1.4 1 Diarrhoea 1.4 1 Ileus 1.4 1 Vomiting 5.7 4 General disorders and administration site conditions 1.4 1 Fatigue 1.4 1 General physical health deterioration 3 1.4 1 Pyrexia 1.4 1 Swelling face 5.7 4 Skin and subcutaneous tissue disorders 4.3 3 Rash maculo - papular 1.4 1 Eczema 4.3 3 Cardiac disorders 4.3 3 Atrial fibrillation 5 2.9 2 Eye disorders 1.4 1 Periorbital oedema 1.4 1 Ulcerative keratitis 2.9 2 Injury, poisoning and procedural complications 1.4 1 Humerus fracture 1.4 1 Infusion related reaction 2.9 2 Musculoskeletal and connective tissue disorders 1.4 1 Back pain 1.4 1 Muscle spasms Adverse event ( System organ class , Preferred term) ≥ Gra 3 No. % tabl continu … 2.9 2 Nervous system disorders 1.4 1 Headache 1.4 1 Posterior reversible encephalopathy syndrome 1.4 1 Endocrine disorders 1.4 1 Inappropriate antidiuretic hormone secretion 1.4 1 Hepatobiliary disorders 1.4 1 Cholangitis 1.4 1 Immune system disorders 1.4 1 Haemophagocytic lymphohistiocytosis 1.4 1 Reproductive system and breast disorders 1.4 1 Vaginal haemorrhage Adverse event ( System organ class , Preferred term) ≥ Gra 3 No. % I MA2 0 3
Best Overall Response for IMA203 in Melanoma Objective Responses in Heavily Pretreated Patients in Phase 1b (N=28 # ) Data cut - off Aug 23, 2024 17 ongoi n g # First tumor assessment post infusion pending for two melanoma patients at data - cut; * Maximum change of target lesions and RECIST1.1 response at different timepoints. **Tumor shrinkage of target lesions; 1 Patient A - DL5 - 23 is off study at data cut - off; 2 Patient out of study due to PD (external assessment); Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with PD at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Overall survival (OS) and progression - free survival (PFS) censored at data - cut; BL: Baseline PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; DCR: Disease control rate, mFU: median follow - up 54% (14/26) cORR 12.1 months (4.2, 25.5+ months) 9.3 months median DOR (min, max) mFU 7/14 confirmed responses ongoing 6.0 months (0.3+, 26.8+ months) median PFS (min, max) Not reached (0.3+, 26.8+ months) 8.6 months median OS (min, max) mFU 62% (16/26) O R R 88% (23/26) Tumor shrinkage ** 92% (24/26) DCR (at week 6) I MA2 0 3
Response Over Time of IMA203 in Melanoma Durable Responses 2 Years+ after Treatment in Heavily Pretreated Patients in Phase 1b (N=28 # ) 18 Ongoing Scans at approximately week 6, month 3 and then every 3 months Data cut - off Aug 23, 2024 # First tumor assessment post infusion pending for two melanoma patients at data - cut; *Tumor shrinkage of target lesions; 1 Patient out of study due to PD (external assessment) 2 Patient A - DL5 - 23 is off study at data cut - off; Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with PD at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Overall survival (OS) and progression - free survi val (PFS) censored at data - cut; BL: Baseline PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; DCR: Disease control rate, mFU: median follow - up 54% (14/26) cORR 12.1 months (4.2, 25.5+ months) 9.3 months median DOR (min, max) mFU 7/14 confirmed responses ongoing 6.0 months (0.3+, 26.8+ months) median PFS (min, max) Not reached (0.3+, 26.8+ months) 8.6 months median OS (min, max) mFU 62% (16/26) O R R 88% (23/26) Tumor shrinkage ** 92% (24/26) DCR (at week 6) I MA2 0 3
Significant Shift in PFS and OS Between Dose Escalation & Dose Expansion PFS of 6 Months and OS Not Reached in Melanoma Efficacy Population 19 Progression Free Survival Data cut - off Aug 23, 2024 Overall Survival Overall survival (OS) and progression - free survival (PFS) censored at data - cut; * These data are derived from different clinical trials at different points in time with differences in trial design and patient populations. As a result, cross - trial comparisons cannot be made, and no head - to - head clinical trials have been conducted. mPFS N 2.6 months 11 Dose Escalation 6.0 months 28 Dose Expansion mOS N 6.3 months 11 Dose Escalation Not reached 28 Dose Expansion Log - rank test: p=<0.0001 Log - rank test: p=0.0003 • Significant shift in PFS and OS between melanoma patients treated during the dose escalation and dose expansion phase • PFS in dose escalation is comparable to reported data in 2L+ cut. melanoma population* • OS in dose escalation is shorter than reported OS for 2L+ cut. melanoma population* • All patients in the dose escalation group died and 20/26 patients are alive in dose expansion I MA2 0 3
IMA203 Phase 1b in Melanoma: Overview of Studies PFS and OS Data in 2L+ Melanoma Cohorts mOS (months) mPFS (months) Prior lines of therapies 2L+ melanoma patient population N Phase Drug Product not reached 6.0 4% n=0, 18% n=1, 32% n=2, 29% n=3:, 4% n=4, 11% n=5, 4% n=6 86% received prior CPI (median of 1 prior line of CPI in overall population, median of 2 prior lines of CPI in cut. melanoma) Median of 2 prior lines, median of 2 prior lines in cut. melanoma 46% cutaneous 43% uveal 11% other 28 1b (Dose Expansion) IMA203 in Melanoma 6.3 2.6 0% n=1, 27% n=2, 73% n>2 prior lines 100% received prior CPI (median of 2 prior lines of CPI, median of 2.5 prior lines of CPI in cut. melanoma) Median of 4 prior lines, median of 4.5 prior lines in cut. melanoma 73% cutaneous 18% uveal 9% other 11 1a (Dose Escalation) IMA203 in Melanoma 5.3 2.5 0% n=1, 16% n=2, 84% n>2 prior lines 100% received prior CPI (median 3 prior lines of CPI) Median of 4 prior lines, median of 4.5 prior lines in cut. melanoma 63% cutaneous 11% uveal 26% other 19 1a (Dose Escalation) IMA201/202/203 combined in Melanoma 13.9 4.1 median of 3 prior lines (min/max: 1/9) 100% received prior CPI 54% cutaneous 0% uveal 45% other 153 2 Lifileucel (C - 144 - 01, Cohort 2+4) 1 11.6 2.9 57% n=1, 27% n=2, 12% n>2 prior lines 99% received prior CPI 85% cutaneous 0% uveal 15% other 238 3 Tilsotolimod + Ipilimumab (ILLUMINATE - 301) 2 14.7 2.1 46% n=1, 35% n=2, 19% n≥3 prior lines 99% received prior CPI 68% cutaneous 0% uveal 32% other 354 1/2 Nivolumab + Relatlimab (RELATIVITY - 020, D1 Cohort) 3 Data cut - off Aug 23, 2024 20 1 Chesney et al., 2022; 2 Diab et al., 2024; 3 Ascierto et al., 2023. These data are derived from different clinical trials at different points in time with differences in trial design and patient populations. As a result, cross - trial comparisons cannot be made, and no head - to - head clinical trials have been conducted. I MA2 0 3
Enhanced PFS in Phase 1b Melanoma Patients with Deep Responses N=26 # 21 • Approx. half of all patients have a deep response (>50% tumor reduction) • This subgroup of patients has highly medically meaningful mPFS of more than 1 year • Patients with <50% tumor reduction (including tumor size increase) still observe a more than 2x longer mPFS as compared to patients treated in dose escalation with suboptimal doses Data cut - off Aug 23, 2024 mPFS N 2.6 months 11 Dose Escalation IMA203 5.7 months 14* Dose Expansion IMA203 <50% tumor size reduction (including tumor size increase) 13.4 months 12 Dose Expansion IMA203 > 50% tumor size reduction # Excluding two patients that were infused but did not have their first tumor assessment post baseline at data - cut; *Includes one patient with ongoing SD 4.4 months after infusion with tumor reduction <50% Log - rank: p=0.0033 I MA2 0 3
0 5 î 10 5 1 î 10 6 1.5 î 10 6 2 î 10 6 2.5 î 10 6 Cmax (vector copies/μg gDNA) 4 6 8 10 Infused Total (CD8 + Dex + ) IMA203 T cell dose (x10 9 ) 2 1 0 Dose Response Relationship IMA203 T Cell Dose is Associated with Clinical Activity and IMA203 T Cell Exposure (N=65 out of 68*) 22 RP2D cPR (n=23) PR or SD or PD (n=42) IMA203 T Cell Dose is Associated with Clinical Activity IMA203 T Cell Dose Correlates with T Cell Exposure 1 Mann - Whitney U test, 2 Spearman Correlation; * no data available yet for patients recently treated; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; , RP2D: recommended phase 2 dose p = 0.0180 1 r=0.8396 p=1.646e - 018 2 Data cut - off Aug 23, 2024 I MA2 0 3
Exposure Response Relationship IMA203 T Cell Persistence Over Time and T Cell Exposure is Associated with Clinical Response 23 Rapid T cell engraftment (C max ) in all patients with over two years of persistence Higher C max and persistence in patients treated at higher doses in dose expansion versus dose escalation cPR P R / S D / P D 1 Mann - Whitney U test; * no data available yet for patients recently treated; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response, AUC: Area under curve Data cut - off Aug 23, 2024 1 1 î 10 2 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 1 î 10 7 2 8 1 4 2 0 2 6 2 8 4 8 6 8 8 8 200 400 600 800 Persistence Overtime Days post infusion Vector copies/ ug gDNA N = 2 7 N = 3 8 Persistence over Time Dose Escalation Dose Expansion N=65 out of 68* N=65 out of 68* IMA203 T cell exposure (C max & AUC (0 - 28d) ) is associated with clinical responses 1 î 10 7 2 î 10 7 3 î 10 7 AUC (0 - 28d) of TCR T Cell Concentration in Blood (vector copies/μg DNA) p = 0.0517 1 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 1 î 10 7 2 8 1 4 2 0 2 6 2 8 4 8 6 8 8 8 200 400 600 800 Days post infusion Vector copies/ ug gDNA I MA2 0 3
Patient Case A - DL4 - 03 : Cutaneous Melanoma 24 Images courtesy of treating physician (Dr. Martin Wermke, University of Dresden) PET - based Complete Response 15 Months Post Infusion and Ongoing Response at 24 Months 51 - year - old male patient with complete remission according to PET imaging after 15 months and ongoing beyond two years post infusion at data cut • 5 prior systemic treatment lines: • Dabrafenib + Trametinib • Pembrolizumab • Dabrafenib + Trametinib + Vemurafenib + Cobimetinib • Tebentafusp • Encorafenib + Binimetinib • 13 years of cancer history • 23 mm target lesion in cervical lymph node and non - target lesions in pelvic bone and lung • Patient received ~1.3x10 9 IMA203 TCR - T cells • Ongoing PR at 24 months post infusion with - 78.3% reduction according to RECIST1.1 • Metabolic complete response reported based on investigator - initiated PET imaging at baseline and month 15 post infusion Follow - up Month 15 Follow - up Month 27 (Post data cut - off) Baseline Follow - up Month 12 Data cut - off Aug 23, 2024 I MA2 0 3
SUPRAME: Registration - enabling Randomized Phase 3 Trial Trial Design Following Recent Type D Meeting with FDA and SA Meeting with PEI 1 25 ACTengine® IMA203 N=180 Investigator’s choice of selected approved treatments N=1 8 0 Endpoints • Primary Endpoint • PFS • Secondary Endpoints • Safety • ORR + DOR • No OS detriment • Patient - reported outcomes (EORTC QLQ - C30, EQ - 5D - 5L) mPFS: median progression - free survival, ORR: objective response rate; 1 Scientific Advice Meeting with Paul - Ehrlich - Institute, the German regulatory authority Randomization 1 : 1 Next Steps • SUPRAME Phase 3 trial is projected to commence in December 2024 • Pre - specified interim analysis planned after approx. 200 patients enrolled • Full enrollment anticipated by late 2026 Patient Population: unresectable or metastatic melanoma post - treatment with a checkpoint inhibitor (2L+) N=360 I MA2 0 3
ACTengine® IMA203 TCR - T Monotherapy Targeting PRAME in Melanoma Summary of Clinical Data Tolerability PFS & OS Biological Data Broad Reach Favorable tolerability profile: mostly mild to moderate CRS; infrequent ICANS (5.7% Gr1, 4.3% Gr2, 4.3% Gr3); no treatment related deaths Anti - Tumor Activity & Durability 54% (14/26) cORR and 92% (24/26) DCR; 12.1 months mDOR and ongoing responses for over two years PFS of 6 months and OS not reached (mFU 8.6 months) T cell dose and exposure are significantly associated with clinical response FDA RMAT designation received in multiple PRAME expressing cancers including cutaneous and uveal melanoma Data cut - off Aug 23, 2024 26 SUPRAME Phase 3 trial is projected to commence in December 2024 I MA2 0 3
27 High Unmet Medical Need in Cutaneous and Uveal Melanoma Clinically and Commercially Attractive Features of IMA203 Uveal Melanoma Cutaneous Melanoma Kim m t r a k - r e f r a c t o r y , CPI/chemotherapy - refractory 2L+ CPI - refractory, BRAF/MEK inhibitor - refractory if BRAF mutation+ 2L+ Patient P o p ul a ti o n ~300 HLA - A*02:01 and PRAME - positive uveal melanoma patients annually in the US 2 ~3,000 HLA - A*02:01 and PRAME - positive cutaneous melanoma patients annually in the US 1 IMA203 Opportunity ≥95% of cutaneous melanoma patients are PRAME - positive Favorable tolerability profile mostly mild to moderate CRS, infrequent ICANS (6% Gr1, 4% Gr2, 4% Gr3), no treatment related deaths Promising anti - tumor activity (cORR, mDOR, PFS) Leukapharesis as source for cell product, no surgery required Short manufacturing time of 7 days plus 7 days of QC release testing Low dose IL - 2 post IMA203 infusion with better tolerability profile than high dose IL - 2 CPI: Checkpoint inhibitor; 1 Based on annual mortality of ~7,700 cutaneous melanoma patients in the US, HLA - A*02:01 prevalence of 41% in the US and PRAME prevalence of 95% (TCGA RNAseq data combined with proprietary MS - guided RNA expression threshold); 2 Based on annual mortality of ~800 uveal melanoma patients in the US, HLA - A*02:01 prevalence of 41% in the US and PRAME prevalence of 89% (IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=33)) Data cut - off Aug 23, 2024 IMA203 in Melanoma Targeted to Enter Randomized Phase 3 Trial in 2L+ Melanoma in 2024 I MA2 0 3
IMA203CD8 GEN2 – IMA203 TCR - T Monotherapy Leveraging CD8 and CD4 cells Differentiated Pharmacology Compared to 1 st - Generation TCR - only Approaches • IMA203CD8 (GEN2) designed to broaden the clinical potential of IMA203 TCR - T monotherapy by adding functional CD4 T cells via co - transduction of CD8αβ alongside PRAME TCR • Activated CD4 T cells aid activity of other immune cells by releasing cytokines and acquire cytotoxic functions • Functional CD4 T cells mediate longer anti - tumor activity than CD8 T cells and potentiate the anti - tumor activity of the cell product in preclinical studies 1 • Data from CD19 CAR - T - treated leukaemia patients suggest a relevant role of engineered CD4 T cells in long - term durability 2 TUMOR CELL DEATH CD4 T CELL Cytotoxic Activity CD8 T CELL T cell Help C y t ot o x ic Activity 28 1 Internal data not shown here, published in Bajwa et al. 2021 Journal for Immunotherapy of Cancer; 2 Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances CD 8 PRAME T CR IMA203CD8
IMA203CD8 (GEN2) – Preclinical Assessment of Anti - Tumor Efficacy Functional CD4 T cells Mediate Longer Anti - Tumor Activity than CD8 T cells in vitro 29 1 .0 1 .5 2 .0 CD 8 0.5 0.0 0 50 100 150 200 250 300 350 400 450 Hours after Coculture Tumor fold growth 2 nd addition of tumor cells 3 rd 4 th 5 th 6 th 2 nd addition of tumor cells 3 rd 4 th 5 th 6 th IMA203CD8
* Patients with at least one available tumor response assessment post infusion; IMA203CD8 DL3: 0.2 - 0.48x10 9 TCR - T cells/m 2 BSA, IMA203CD8 DL4a: 0.481 - 0.8x10 9 TCR - T cells/m 2 BSA, All Comers N=12 Efficacy population* 3 (1, 5) Prior lines of systemic treatment (median, min, max) 50.0 LDH at baseline >1 x ULN [% of patients] 79.8 (20.0, 182.0) Baseline tumor burden Median target lesion sum of diameter [mm] (min, max) DL3/DL4a/DL4b Dose level Data cut - off Sep 30, 2023 30 IMA203CD8 (GEN2) – Overview of Patient Characteristics Data cut - off as of Sep 30, 2023 Phase 1b Dose Expansion (N=12) DL 3/4a/4b DL4a cleared 1 IMA203CD8 IMA203CD8 DL4b: 0.801 - 1.2x10 9 TCR - T cells/m 2 ; 1 DL4a cleared in Dec 2023
Tolerability Data – IMA203CD8 (GEN2) 31 % No. ( System organ class , preferred term) 100.0 12 Patients with any adverse event 25.0 3 Adverse events of special interest 25.0 3 Cytokine release syndrome 1 0.0 0 Immune effector cell - associated neurotoxicity syndrome 91.7 11 Blood and lymphatic system disorders 75.0 9 Neutropenia 66.7 8 Anaemia 66.7 8 Lymphopenia 33.3 4 Thrombocytopenia 16.7 2 Leukopenia 33.3 4 Investigations 16.7 2 Aspartate aminotransferase increased 16.7 2 Neutrophil count decreased 8.3 1 Alanine aminotransferase increased 8.3 1 Blood alkaline phosphatase increased 8.3 1 Blood bilirubin increased 8.3 1 Gamma - glutamyltransferase increased 16.7 2 Metabolism and nutrition disorders 8.3 1 Hypermagnesaemia 8.3 1 Hypoalbuminaemia 8.3 1 Hypophosphataemia 16.7 2 Nervous system disorders 8.3 1 Neurotoxicity 2 8.3 1 Syncope 8.3 1 Immune system disorders 8.3 1 Haemophagocytic lymphohistiocytosis 2 8.3 1 Infections and infestations 8.3 1 Infection All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient (except for ICANS, where no event was documented; listed for completeness due to being an adverse event of special interest) are presented. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 5.0. Grades for CRS and ICANS were determined according to CARTOX criteria (Neelapu et al., 2018). Patients are counted only once per adverse event and severity classification. Based on interim data extracted from open clinical database (30 - Sep - 2023); 1 DLT: Dose limiting toxicity in patient DL4b - 04. 2 DLTs in patient DL4b - 01; ll ≥Gra 3 v rs v nts (N=12) TEAEs by maximum severity for all patients (N=12) Adverse event ≥ Gra 3 • Manageable tolerability • Most frequent ≥Grade 3 AEs were expected cytopenia associated with lymphodepletion • No IMA203CD8 - related Grade 5 Adverse Events 1 • Dose escalation ongoing Data cut - off Sep 30, 2023 1 Subsequent to data cut - off a Grade 5 event, possibly related to treatment, was observed. The patient’s immediate cause of death was considered to be fatal sepsis, aggravated by the immunosuppression, a high - grade Immune Effector Cell - Associated Hemophagocytic Lymphohistiocytosis - Like Syndrome (IEC - HS), and the fast - progressing disease. IMA203CD8
IMA203CD8 (GEN2) (N=12 # ) – BOR and Response over Time Data cut - off Sep 30, 2023 • 6 out of 7 responses ongoing • 11/12 patients show tumor shrinkage • Deepening of response from SD to PR in two patients (C - DL4a - 01, C - DL4a - 03) • Ongoing durable response 12+ months after infusion Not reached, 2.0+, 11.5+ months Median DOR, min, max DOR 4.8 months Median Follow - up 58% (7/12) ORR 56% (5/9) cORR Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with progressive disease (PD) at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Median Follow - up is analyzed by using the reverse Kaplan - Meier method; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline; BOR: Best Overall Response; DOR: Duration of Response # Patient C - DL4a - 04 was PD ~6 weeks after infusion, not shown due to non - evaluable target lesions at tumor assessment Ongoing Scans at approximately week 6, month 3 and then every 3 months Data cut - off Sep 30, 2023 32 * Clinical tumor progress after 4.9 months post infusion, investigator information * IMA203CD8
IMA203CD8 (GEN2): Translational Data Shows Enhanced Pharmacology IMA203 Phase 1b vs IMA203CD8 (GEN2) Trend towards responses at lower cell dose and higher tumor burden with IMA203CD8 Higher peak expansion (C max ) of IMA203CD8 T cells when normalized to infused dose Higher activation levels in IMA203CD8 T cells at week 1… …without exhaustion over time Initial translational data indicates higher biological and clinical activity of IMA203CD8 (GEN2) %PD - 1 of specific T cells at week 1: for patient A - DL5 - 05 data not available for week 1 5 î 1 0 5 0 1 î 10 6 1.5 î 10 6 2 î 10 6 2.5 î 10 6 Vector copies/μg gDNA p = 0.001 0 P D /SD PR cPR Cohort A I M A 203 GEN1 Cohort C I M A 203 CD 8 GEN2 Data cut - off Sep 30, 2023 33 IMA203CD8 IMA203CD8 (GEN2) IMA203CD8 (GEN2) IMA203 IMA2 0 3 C D8 (GEN2) I M A203 IMA203 IMA203CD8 IMA203 (GEN2)
ACTengine® IMA203CD8 (GEN2) TCR - T Monotherapy Targeting PRAME Summary of IMA203CD8 Clinical Data and Planned Next Steps • Enhanced primary and secondary pharmacology when compared to IMA203 • Manageable tolerability (2 DLTs at DL4b, dose escalation ongoing) • Initial clinical activity observed with differentiated response pattern • 56% (5/9) cORR • 6 out of 7 responses ongoing at data cut - off, durable response at 12+ months • SD converting to PR over time (N=2) • Enhanced biological efficacy with PRs at lower T cell:tumor cell ratio compared to IMA203 34 Next Step Clinical footprint expansion outside of melanoma in addition to treating melanoma patients Data cut - off Sep 30, 2023 IMA203CD8
PRAME mRNA expression in IMA203 Phase 1a and Phase 1b responders at RP2D (n=13) PRAME mRNA expression in IMA203CD8 (GEN2) responders (n=7) Potential of IMA203 in Additional Solid Cancer Indications % PRAME - positive patients 1 PRAME target expression distribution (blue histogram) based on TCGA RNAseq data, patient data (black dots) based on IMADetect® qPCR testing of screening biopsies; 1 PRAME target prevalence is based on TCGA RNAseq data combined with a proprietary MS - guided RNA expression threshold; 2 PRAME target prevalence in uveal melanoma based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=33) demonstrates substantial higher Data cut - off Sep 30, 2023 35 ≥95% ≥91% (50% 2 ) 97% 100% 84% 68% 63% 27% Immatics’ current MS - guided mRNA threshold for patient selection Selected indications Clinical activity shown No clinical activity expected Based on PRAME Expression in IMA203 and IMA203CD8 (GEN2) Responders Potential opportunity to see clinical activity IMA203 prevalence of 91% compared to prevalence based on TCGA data of 50%, TCGA: early & late - stage primary tumor samples, Immatics clinical trials: late - stage/metastatic tumor samples, Role of PRAME in metastasis of uveal melanoma: Field et al. 2016 Clinical Cancer Research; MS: mass spectrometry
36 ACTengine® IMA203 / IMA203CD8 TCR - T Monotherapy Targeting PRAME Leveraging the Full Breath of PRAME in Three Steps Development Strategy Step 1 IMA203 in cutaneous melanoma as first tumor type targeted to enter registration - enabling trial in December 2024 Further dose escalation in melanoma followed by signal finding in ovarian cancer and uterine cancer in dedicated dose expansion cohorts with IMA203CD8 (GEN2) Pursue tumor - agnostic label in PRAME+ solid cancers to leverage full breadth of PRAME - including NSCLC, triple - negative breast cancer and others Step 2 Step 3 I MA2 0 3
TCER® – TCR Bispecifics 37
TCER® – Immatics’ N xt - generation, Half - Life Extended Bispecifics Proprietary TCER® Format Consisting of Three Distinct Elements 38 High - affinity TCR domains targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules L o w - a ffi n i t y T cell recruiter against CD3/TCR Fc part for half - life extension, favorable stability and m a nu f a c t u r a b ility Next - gen, half - life extended TCER® format designed to safely apply high drug doses for activity in a broad range of tumors achieve optimized scheduling 2 1 3 C y t o t o x ic lytic granules Tumor cell killing Activated T cell T CE R®
TCER® – Immatics’ N xt - generation, Half - Life Extended Bispecifics 39 pHLA targeting TCR x High - affinity (single digit nM) TCR targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules x Broad therapeutic window through XPRESIDENT® - guided affinity maturation (>1000x) 1 x Complete tumor eradication in mouse xenograft models at low doses T cell recruiting antibody x Low - affinity (triple digit nM) T cell recruiter against both TCR & CD3 x Optimized biodistribution aiming for enrichment at tumor site and prevention of CRS 2 x Superior anti - tumor activity in mouse models as compared to widely used CD3 recruiters Next - generation TCER® format x Off - the - shelf biologic with antibody - like manufacturability 3 and low cost of goods x Superior anti - tumor activity 4 compared to six alternative bispecific formats x Half - life of several days expected in humans Our TCER® format is designed to maximize efficacy while minimizing toxicities in patients 1 As compared to natural TCR; 2 Based on literature data for other low - affinity recruiters (e.g. Harber et al ., 2021, Nature; Trinklein et al ., 2019, mAbs); 3 Production in mammalian cells (CHO cells); 4 Based on preclinical testing T CE R® 1 2 3
Potency of Our Proprietary TCR Bispecific Format TCER® 40 • Seven different TCR Bispecific formats were evaluated with a pHLA targeting TCR and the identical T cell recruiting antibody • TCER® format had higher combination of potency and specificity 2 than six alternative TCR Bispecific format designs evaluated Flexible Plug - and - play platform: TCER® format successfully validated for different TCRs & different T cell recruiting antibodies T C E R ® 2+1 TCR bispecific format: High potency was linked to a significantly reduced specificity profile 2 Killing of target - positive cells by different TCR Bispecifics 1 1 Data presented at SITC 2022; 2 Preclinical data on specificity not shown T CE R®
TCER® Format Is Designed for Optimized Efficacy and Safety Superior Tumor Control Using a Novel, Low - Affinity Recruiter 41 n = 6 mice/treatment group, n = 10 mice in vehicle group, 2 donors/group Dose : 0 . 025 mg/kg Proprietary, low - affinity T cell recruiting region demonstrates superior tumor control compared to analogous TCER® molecules designed with higher - affinity variants of a widely used recruiter Widely used T cell recruiting Ab (3 variants) medium to high affinity (single to double digit nM) Immatics’ c ll r cruiting b low affinity (triple digit nM) T CE R® Tumor Model in Mice 1 1 Hs695T xenograft model in NOG mice, tumor volume of group means shown
TCER® Format Is Designed for Optimized Efficacy and Safety Reduced Target - Unrelated Recruiter - Mediated Cytokine Release using a Low - Affinity Recruiter 42 T CE R® Whole blood cytokine release assay N=3 HLA - A*02 - positive donors N=16 cytokines tested, 4 exemplary cytokines shown
Our TCER® Portfolio Broad Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 43 T CE R® • PRAME peptide presented by HLA - A*02:01 • Start of clinical trial in Aug 2023, first clinical data expected 2H 2024 IMA402 Potential for addressing different indications and large patient populations with novel, off - the - shelf TCR Bispecifics • MAGEA4/8 peptide presented by HLA - A*02:01 • Dose escalation ongoing, first clinical data presented at ESMO 2024 IMA401 • Undisclosed peptides presented by HLA - A*02:01 and other HLA - types • TCER® engineering and preclinical testing ongoing IMA40x Several innovative programs CLINICAL PRECLINICAL The current collaboration with Moderna includes the development of mRNA - enabled in vivo expressed TCER® molecules
In Vivo Expressed TCER® Molecules Targeting Cancer - specific pHLA Targets ombining Immatics’ arg t an latforms with o rna’s m N chnology 44 Moderna Delivery of TCER® biologics through mRNA Immatics Proprietary cancer targets & TCR Bispecifics format mRNA - encoded TCER® molecule XPR E SIDENT® targets X CE P T O R® TCRs TCER® f o r m a t T CE R®
TCER® IMA401 Targeting MAGEA4/8 45
TCER® IMA401 Targeting MAGEA4/8 Higher Target Density of MAGEA4/8 Peptide 46 MAGEA4 protein detection in tumor samples (IHC) 1 MAGEA4/8 target prevalences are based on TCGA and in - house data combined with a XPRESIDENT® - determined target individual MS - based mRNA expression threshold; qPCR - threshold for patient screening; 2 Students paired T test; 3 Copy number per tumor cell (CpC) measured on a paired - sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/8 peptide presentation on same sample p<0.001 2 MAGEA4/8 target is presented at >5 - fold higher target density 3 than a commonly used MAGEA4 target peptide HNSCC sq. NSCLC 100 µm MAGEA4/8 target prevalence in selected cancer indications Number of addressable patients* Target prevalence 1 [%] Indications 22k 52% Squamous non - small cell lung carcinoma 7k 36% Head and neck squamous cell carcinoma 9k 29% Bladder carcinoma 4k 23% Ovarian carcinoma 3k 23% Esophageal carcinoma 4k 21% Small cell lung cancer 2k 20% Triple - negative breast cancer 3k 14% Gastric adenocarcinoma 2k 18% Cutaneous melanoma 6k 9% Non - small cell lung adenocarcinoma *1L+ Unresectable or Metastatic Addressable Patient Populations (US, UK, EU4 in 2025), total MAGE A4/A8+ and HLA - A*02+ I MA4 0 1
TCER® IMA401 (MAGEA4/8) – Assessment of Anti - Tumor Activity in vitro Patient - Derived Tumor Model 47 NSCLC adenocarcinoma: • Male, Caucasian, age 58, no therapy prior to surgery • Site of origin: lung, differentiation poor • Date of surgery: 1987, Freiburg Medical Center • Volume doubling time: 7.3 day • Histology: • Stroma content, 4% • Vascularization, high • Grading, undifferentiated • TCER® IMA401 shows high anti - tumor activity in Patient - derived xenograft model of non - small cell lung adenocarcinoma • Remission observed in all mice (3 out of 4 mice with complete remission) LXFA 1012 Tumor Xenograft Model in NOG Mice I MA4 0 1
48 180 µg 540 µg 1800 µg 2500 µg Key Eligibility Criteria Object iv es Primary: • Determine MTD and/or RP2D Secondary: • Tolerability • Pharmacokinetics • Initial anti - tumor activity • Recurrent and/or refractory solid tumors • HLA - A*02:01 positive • MAGEA4/8 - positive as confirmed by mRNA - based assay 3 • ECOG status 0 - 2 • Received or not eligible for all available indicated standard of care treatments 60 µg 1200 µg 20 µg 6.6 µg • MTD not yet determined • Dose escalation ongoing to optimize dosing intervals and schedule Total safety population (N=35) • MABEL - based starting dose • Dose escalation based on cohorts of 1 - 6 patients using adaptive design (BLRM model) • Four initial q1w step dosings 1 up to target dose, q2w after reaching target dose 2 Trial Design – IMA401 - 101 Phase 1a Dose Escalation First - in - Human Basket Trial Targeting the MAGEA4/8 Peptide in Solid Tumors 1 Step dosing with 300 µg and 600 µg introduced at DL6; Low - dose dexamethasone pre - medication used at higher dose levels as used with other approved bispecific products has been implemented as preventive measure for continued dose escalation; Patients can increase their dose to previously cleared dose levels; 2 q2w: once every two weeks, weekly (q1w) dosing was applied up to DL5; 3 IMADetect®: proprietary mRNA - based assay using Immatics’ MS - guided threshold; BLRM: Bayesian logistic regression model; MTD: Maximum tolerated dose. D L1 D L2 D L3 D L4 D L5 D L6a D L7 D L6 t bd 2000 µg D L6b Data cut - off Jul 23, 2024 I MA4 0 1
Baseline Characteristics Heavily Pre - treated Patients with a Broad Range of Tumor Types 49 1 Efficacy Analysis Set (EAS) prospectively defined in the study protocol: patients who received at least four IMA401 infusions and had at least one post - baseline efficacy assessment or clinical progression. Three patients did not receive all four infusions due to clinical progression and three patients awaiting their first scans as of the data cut - off date are not included in the EAS; 2 Patients in Data cut - off Jul 23, 2024 this analysis had received IMA401 infusions at ≥1 mg and showed MAGEA4/8 target expression higher than the MAGEA4/8 qPCR threshold. LDH: Lactate dehydrogenase; ULN: Upper limit of normal. Patients with relevant IMA401 doses and MAGEA4/8 high levels 2 N=17 Efficacy - evaluable Population 1 N=29 Safety Population N=35 Characteristic 64 (35, 82) 63 (35, 82) 62 (19, 82) Age Median (min, max) 3 [17.6] 12 [70.6] 2 [11.8] 6 [20.7] 21 [72.4] 2 [6.9] 10 [28.6] 23 [65.7] 2 [5.7] ECOG performance status 0 - n [%] 1 - n [%] 2 - n [%] 4 (2, 8) 3 (2, 8) 4 (2, 8) Prior lines of systemic treatment Median (min, max) 41.2 58.8 0.0 55.2 41.4 3.4 51.4 40.0 8.6 LDH at baseline ≤ 1xULN [%] 1 - 2xULN [%] > 2xULN [%] 84 (18, 202.8) 80 (15, 202.8) 74 (15, 202.8) Baseline tumor burden Median target lesion sum of diameter [mm] (min, max) 3 (1, 6) 3 (1, 6) 3 (1, 6) Number of organs with metastases Median (min, max) 47.1 41.4 40.0 Liver/ Brain Lesions [% of patients] I MA4 0 1
50 IMA401 Demonstrates Manageable Tolerability in N=35 Patients Most Frequent Related AEs were Lymphopenia, CRS and Neutropenia ≥ Gra 3 All Grades TEAEs, n [%] 26 [74] 32 [91] Any 19 [54] 28 [80] Treatment - related ≥ Gra 3 All Grades Treatment - related AEs 1 , n [%] 11 [31] 12 [34] Lymphopenia 0 11 [31] Cytokine release syndrome 5 [14] 8 [23] Neutropenia 2 [6] 6 [17] Facial pain 4 [11] 5 [14] Anaemia 2 [6] 5 [14] Thrombocytopenia 1 [3] 5 [14] Headache 2 [6] 4 [11] Hypertension 2 [6] 4 [11] Leukopenia 0 4 [11] Fatigue 0 3 [9] Nausea 1 [3] 2 [6] Hypoxia 1[3] 1 [3] Aspartate aminotransferase increased 1[3] 1 [3] Febrile neutropenia 1[3] 1 [3] Pneumonia 1[3] 1 [3] Sinus tachycardia • Overall manageable tolerability profile • Most frequent/relevant related AEs were • transient lymphopenia, • mild to moderate CRS (23% Grade 1, 9% Grade 2, no Gra ≥ 3 ), majority at first dose • neutropenia 2 occurred mostly at initial target dose and fully resolved in all cases except one (see below) • one possibly related death (pneumonia in the context of lung tumor progression and concurrent neutropenia) as previously reported 3 • MTD not reached based on the BLRM 1 All treatment - emergent adverse events (TEAEs) at least possibly related to IMA401 infusion with grade 1 - 2 occurring in at least 9% of patients and all events with grade 3 - 5; 2 with three dose - limiting events at 2.5 mg (DLT), neutropenia observed in patients with and without dexamethasone pre - medication; 3 reported in Annual Report 2023, patient did not receive dexamethasone pre - medication; CRS: Cytokine Release Syndrome; BLRM: Bayesian logistic regression model; MTD: Maximum tolerated dose. Data cut - off Jul 23, 2024 I MA4 0 1
IMA401 Pharmacokinetics TCER® Format Shows Extended Half - Life in Solid Cancer Patients 1 Half - lifes derived from 2nd PK profiles close to steady - state. Calculated by non - compartmental analysis (NCA) using Phoenix WinNonlin (Certara); Interquartile range (25% - 75% percentile): 13.5 - 22.2 days; 2 Data presented at European Antibody Congress 2020; Zinn et al., Nature Cancer , 2023: https://doi.org/10.1038/s43018 - 023 - 00516 - z; LLOQ: lower limit of quantification; q4w: once every four weeks. CPI: Checkpoint inhibitor Median half - life: 16.9 days (N=16) 1 Slow elimination Days post 4 th infusion IMA401 serum conc. [ng/mL] 6.6 µg 20 µg 60 µg 180 µg LL OQ 324 µg 540 µg 1,200 µg PK profiles (1 week profiles after 4 th IMA401 infusion) Observed T 1 / 2 > 2 weeks • Confirms “antibody - like” half - life predicted by preclinical in - vivo data 2 • Supports exploring increased dosing intervals of up to q4w and pursuing alignment with typically applied CPI dosing regimens Data cut - off Jul 23, 2024 I MA4 0 1
1 Patients in this analysis had received IMA401 infusions at ≥1 mg and showed MAGEA4/8 target expression above indicated MAGEA4/A8 high qPCR threshold (n=17); PD: Progressive disease; PR: Partial response; cPR: confirmed Partial response; SD: Stable disease. 52 Data cut - off Jul 23, 2024 Objective Responses are Associated with Target Expression Exploratory Analysis in Patients with MAGEA4/8 high Expression at Relevant IMA401 Doses (DL6 - 7; N=17) qPCR - threshold MAGEA4/8 high qPCR - threshold for patient screening MAGEA4/8 RNA expression in pre - treatment biopsies relative to t h r es ho ld N=17 patients with relevant IMA401 doses and MAGEA4/8 high levels 1 I MA4 0 1
53 *Patients in this analysis are part of the efficacy analysis set with at least one post - treatment tumor assessment and had received IMA401 infusions at ≥1 mg and showed MAGEA4/8 target expression higher than the MAGEA4/8 qPCR threshold (n=17); Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with progressive disease (PD) at any prior timepoint; two patients not included in tumor shrinkage calculation or shown in the figures as they had clinical progression and post - treatment tumor assessment is not available; PR: Partial Response; cPR: Confirmed Partial Response; SD: Stable Disease. Data cut - off Jul 23, 2024 11 12 13 14 - 1 0 0 - 5 0 0 50 1 0 0 Change in Sum of Longest Diameter of Target Lesions from Baseline [%] ⯈ BL PR PD ⯈ ⯈ ⯈ ⯈ ⯈ Target Lesion r e s e c t e d ⯈ ⯈ IMA401 Demonstrates Initial Anti - Tumor Activity in Multiple Tumor Types Exploratory Analysis in Patients with MAGEA4/8 high Expression at Relevant IMA401 Doses (DL6 - 7; N=17*) 29% (5/17) ORR 25% (4/16) cORR 53% (9/17) DCR 53% (8/15) Tumor s h rin k a g e Cancer indications 0 1 2 3 4 5 6 7 8 9 10 Months post First IMA401 Infusion Cancer Indications: Cut.: Cutaneous; HNSCC: Head & Neck Squamous Cell Carcinoma; LCNEC: Large Cell Neuroendocrine Carcinoma; Muc.: Mucosal; NET CUP: Neurodendocrine Tumor, Cancer of Unknown Primary; SCLC: Small Cell Lung Cancer; sqNSCLC: Squamous Non - small Cell Lung Cancer; TNBC: Triple Negative Breast Cancer. BOR (RECIST 1.1) Ongoing treatment I MA4 0 1
Clinical Activity in Heavily Pre - Treated Cancer Patients 54 CT and MRI scans courtesy of treating physicians (Dr. Manik Chatterjee, University Hospital Wuerzburg and Dr. Max - Felix Häring, Eberhard Karls University Tuebingen); HNSCC: Head and neck squamous cell carcinoma; NET CUP: Neuroendocrine tumor - cancer of unknown primary; LA: Long axis; cPR: confirmed Partial response; BOR: Best overall response Baseline MRI Follow Up Week 13 Outcomes Patient Characteristics cPR - 56% reduction (BOR: - 58.6%) NET CUP cPR ongoing at week 36 post - treatment start Lesions in liver, lung, bone, pancreas, adrenal gland, lymph nodes 4 prior lines of therapy: Two lines of radiopharmaceuticals, chemotherapy, mTOR inhibitor 60 - year - old female, NET CUP, MAGEA4/8 high 63 - year - old male, HNSCC, MAGEA4/8 high Outcomes Patient Characteristics cPR - 59% reduction HNSCC, Hypopharynx cPR ongoing at week 12 post - treatment start Lesions in lung 3 prior lines of therapy: Platinum chemotherapy, anti - PD - 1/chemotherapy, anti - EGFR/chemotherapy LA: 18mm LA: 21mm LA: 70mm LA: 34mm Data cut - off Jul 23, 2024 Baseline CT Follow Up Week 13 Lung right Lung left LA: 6mm LA: 10mm I MA4 0 1
First - in - human Data of IMA401 TCER® Targeting MAGEA4/8 Presentation at ESMO on September 16, 2024 • Tolerability : Most common treatment - related AEs are low - grade CRS, transient lymphopenia and neutropenia • Pharmacokinetics : Median terminal half - life of 16.9 days supporting potential further flexibility in future dosing schedules incl. combination with CPI and increased dosing intervals up to q4w • Initial anti - tumor activity in heavily pre - treated patients • Objective responses in HNSCC, neuroendocrine tumor of unknown origin, cutaneous and mucosal melanoma including durable ongoing PRs of up to 13+ months • Deep responses (tumor shrinkage of ≥ 50%) in four patients including deepening of responses over time • Objective responses are associated with target expression and IMA401 dose: ORR 29%, cORR 25%, and tumor shrinkage in 53% of patients with relevant IMA401 doses and MAGEA4/8 high target levels • Dose escalation ongoing 55 AE: Adverse Event; CRS: Cytokine Release Syndrome; CPI: checkpoint inhibitors; q4w: once every four weeks; HNSCC: Head and neck squamous cell carcinoma; PR: Partial Response
TCER® IMA402 Targeting PRAME 56
TCER® IMA402 Targeting PRAME – Efficacy Assessment in vitro Tumor Cell Killing at Low Physiological PRAME Peptide Levels 57 140 120 100 80 60 40 20 0 ~50 PRAME CpCs 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] Cytotoxicity [%] Target - negative 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~110 PRAME CpCs 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~250 PRAME CpCs 0 • TCER® IMA402 induces killing of tumor cells with PRAME target copies as low as 50 CpCs • Physiological PRAME levels detected in majority of cancer tissues from patients are 100 – 1000 CpCs • Preclinical activity profile enables targeting of a broad variety of tumor indications, such as lung cancer, breast cancer, ovarian cancer, uterine cancer, melanoma and others I MA4 0 2 CpC: Target peptide copy numbers per tumor cell
TCER® IMA402 Achieves Durable Tumor Control of Large Tumors in vivo 58 • Dose - dependent efficacy of IMA402 in cell line - derived in vivo mouse model • Durable shrinkage of large tumors including complete responses over prolonged period • Sufficiently high drug doses are key to achieving desired anti - tumor effect I MA4 0 2
Half - life Extended Format of IMA402 Confers Terminal Half - life of >1 Week 59 pHLA – aFc Assay pHLA – aV L Assay • IMA402 shows a terminal serum half - life of ≈ 8 days in mice • IMA402 will be initially dosed weekly in the clinical trial • Dosing frequency may be adapted based on clinical data I MA4 0 2
Phase 1/2 Clinical Trial to Evaluate TCER® IMA402 Targeting PRAME First Clinical Data Planned in 2H 2024 60 Phase 1: Dose Escalation Phase 2a: Dose Expansion Adaptive design aimed at accelerating dose escalation • Specific indications plus ongoing basket • Combination therapies • Optional dose/application optimization Expansion cohort Expansion cohort Expansion cohort Trial Overview Phase 1/2 clinical trial to evaluate safety, tolerability and anti - tumor activity of IMA402 • HLA - A* 02 : 01 - positive patients with PRAME - expressing recurrent and/or refractory solid tumors • Initially weekly i . v . infusions • Potential for early adjustment of treatment interval based on PK data of half - life extended TCER® format MTD/ RP2D I MA4 0 2 • Basket trial in focus indications to accelerate signal finding • Ovarian cancer, lung cancer, uterine cancer, melanoma, others MTD: maximum tolerated dose, RP2D: recommended phase 2 dose
Immatics’ ro ri tary arg t an Discov ry latforms 61
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 62 Technology
True Cancer Targets & Matching Right TCRs Goal to Maximize Anti - Tumor Activity and Minimize Safety Risks of TCR - based Immunotherapies 63 True Targets via XPRESIDENT® technology platform • are naturally presented on tumor tissues as identified by mass - spec • are absent or presented at only low levels on normal tissues • are presented at high copy numbers to trigger a pharmacological response + Technology Right TCRs via XCEPTOR® technology platform • recognize the target peptide with high affinity and specificity • show selective killing of tumor cells • are developed to be suitable for two different therapeutic modalities, Cell Therapies and TCR Bispecifics
Technology Pool of 200 Prioritized Targets as Foundation for Future Value Generation XPRESIDENT® Target Platform 64 200 Prioritized Targets Grouped in 3 Target Classes: 1. Well known and characterized parent protein (20%) e.g. MAGE family cancer testis antigens 2. Unknown or poorly characterized parent protein (60%) e.g. stroma target COL6A3 exon 6 3. Crypto - targets/Neoantigens (20%) Novel target class which includes RNA - edited peptides & non - classical neoantigens ~50% of our prioritized targets are non - HLA - A*02 restricted, substantially broadening the potential patient reach e >2,500 cancer & normal tissues analyzed by Quantitative, Ultra - Sensitive Mass Spectrometry pHLA Database based on primary tissues >200 prioritized targets This large data set is leveraged by our bioinformatics & AI - platform XCUBE – „AI is where the data is®“
Potential for Large Patient Populations across Multiple Solid Cancers 65 Uterine Carcinoma – 97% Uterine Carcinosarcoma – 100% Sarcoma Subtypes – up to 100% Cut. Melanoma – 95% Uveal Melanoma 1 – 89% Ovarian Carcinoma – 84% Squamous NSCLC – 68% TNBC – 63% Small Cell Lung Cancer – 45% Kidney Carcinoma – up to 40% Cholangiocarcinoma – 33% HNSCC – 27% Esophageal Carcinoma – 27% Breast Carcinoma – 26% Adeno NSCLC – 25% HCC – 18% Bladder Carcinoma – 18% Squamous NSCLC – 52% Sarcoma Subtypes – up to 60% HNSCC – 36% Bladder Carcinoma – 29% Uterine Carcinosarcoma – 29% Esophageal Carcinoma – 23% Ovarian Carcinoma – 23% Melanoma – 18% IMA203 / IMA402 PRAME IMA401 M A G E A 4/8 IMA204 COL6A3 Exon 6 ACTengine® and TCER® targets demonstrate high prevalence in multiple solid cancers Target prevalence for selected solid cancer indications are based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; 1 Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=61) Pancreatic Carcinoma – 76% Breast Carcinoma – 77% Stomach Carcinoma – 67% Sarcoma – 63% Colorectal Carcinoma – 60% Esophageal Carcinoma – 60% Squamous NSCLC – 55% Adeno NSCLC – 57% HNSCC – 56% Uterine Carcinosarcoma – 50% Mesothelioma – 44% Cholangiocarcinoma – 36% Melanoma – 35% Bladder Carcinoma – 34% Ovarian Carcinoma – 31% Technology
Immatics’ Uniqu a ability – Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target 66 1 Copy number per tumor cell (CpC) measured on a paired - sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/A8 peptide presentation on same sample, 2 Students paired T test p<0.001 2 Technology MAGEA4/8 target is presented at >5 - fold higher target density 1 than a commonly targeted MAGEA4 target peptide XPRESIDENT® quantitative information on target density 1 between peptides originating from the same source protein Ranking of pHLA targets Co mmonly targeted
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 67 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy A C T e n g in e ® ACTallo® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Protein engineering capabilities to design and maturate TCRs with increased affinity while retaining specificity • Early de - selection of cross - reactive TCRs by the unique interplay between Immatics’ target and TCR discovery platforms XPRESIDENT® and XCEPTOR® during TCR discovery 1 and TCR maturation 2 (empowered by our bioinformatics & AI - platform XCUBE ) Micromolar affinity Nanomolar affinity Technology 1 XPRESIDENT® - guided off - target toxicity screening; 2 XPRESIDENT® - guided similar peptide counterselection
Optimal Target Selection & TCR Specificity for Minimizing Safety Risks Unique Interplay between Technology Platforms Allows Early De - risking for Clinical Development 68 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Of f - t a r ge t toxicity On - target (off - tumor) toxicity A different HLA is recognized on normal cells Alloreactivity Similar peptide presented on normal cells 1 XPRESIDENT® - guided screening for on - and off - target toxicities of TCRs based on the extensive database of peptides presented on normal tissues Technology 1 Clinical fatalities have occurred in TCR - T trials using a titin cross - reactive TCR (Cameron et al ., Sci Transl Med)
“ I Is Wh r th Data Is®” Bioinformatics and AI - Platform XCUBE 69 Data Engineering Development of data warehouses & user interfaces Data Science Development of statistical & machine learning models Data Processing Processing of mass - spec & next - gen sequencing data 1 THE RA PE U TIC KNOWLEDGE XPRESIDENT®/ XCEPTOR® DATA Data Engin e e r i n g Data Sci e n c e Data P r o c ess i ng 2 3 1 Cell therapies Bispecifics CDx Therapies Lead Molecules Discovery C h a r a c t eri z a tion Targets Discovery Selection V alid a tion 2 3 Technology
Immatics’ obust Int ll ctual ro rty ortfolio Protection Strategy of Key Assets in Major Markets and Beyond 70 Technologies T ar g e ts T CRs T C ER® Th e r ap e u t ic Uses Cell Therapy TCRs with high affinity and specificity profile Differentiated technologies, platforms and assays for Target Research, TCR and TCER® development >200 prioritized pHLA targets Half - life extended Bispecifics with proprietary TCER® format Treatment of indications and patient groups Clinical ACTengine® and TCER® candidates: IMA203, IMA203CD8, IMA402, IMA401 Clinical Ca ndid a t e s ACTengine® manufacturing & off - the - shelf ACTallo® platform Technology
ACTengine® IMA204 – TCR - T Targeting COL6A3 Exon 6 71
ACTengine® IMA204 First - in - Class TCR - T Targeting Tumor Stroma Key Features 72 HLA - A*02 - presented peptide derived from COL6A3 exon 6 Naturally and specifically presented on tumors at high target density 1 : 100 - 700 copies/cell Novel tumor stroma target identified and validated by XPRESIDENT® quant. mass spectrometry platform High - affinity, specific TCR targeting COL6A3 exon 6 Affinity - maturated, CD8 - independent TCR High functional avidity 2 : ~0.01ng/ml Identified and characterized by XCEPTOR® TCR discovery and engineering platform CD8 - independent, next - generation TCR engages both, CD8 and CD4 T cells In vitro anti - tumor activity against target - positive cell lines in CD8 and CD4 T cells Complete tumor eradication in in vivo mouse models Pancreatic Carcinoma – 76% Breast Carcinoma – 77% Stomach Carcinoma – 67% Sarcoma – 63% Colorectal Carcinoma – 60% Esophageal Carcinoma – 60% Squamous NSCLC – 55% Adeno NSCLC – 57% HNSCC – 56% Uterine Carcinosarcoma – 50% Mesothelioma – 44% Cholangiocarcinoma – 36% Melanoma – 35% Bladder Carcinoma – 34% Ovarian Carcinoma – 31% 1 Target density: peptide copy number per tumor cell, approximate range representing the majority of tumor samples analyzed; 2 Functional avidity: EC50 half maximal effective concentration; 3 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data) T A R GET T CR PRECLINICAL DATA PATIENT POPULATION 3 IMA204 provides a promising therapeutic opportunity for a broad patient population as monotherapy or in combination with TCR - T cells directed against tumor targets I MA2 0 4
ACTengine® IMA204 – High Affinity, CD8 - independent TCR Complete Tumor Eradication in vitro & in vivo 1 by Affinity - enhanced IMA204 TCR CD8 - independent TCR leads to tumor eradication in all mice treated 73 W Si Do ild t ngl ub l y pe e m e m utan u t a n t t T u No mo n - t r ce ran lls o s duc n l y ed Co n t r ol IMA204 TCR D7 D16 D22 D29 Affinity maturated CD8 - independent, next - generation TCR engages both CD4 and CD8 T cells without the need of CD8 co - transduction S tr o ma cells T umo r cells Stroma Target (COL6A3 exon 6) in Ovarian Cancer sample Example of a Tumor Target in same Ovarian Cancer sample 1 In vivo data in collaboration with Jim Riley, University of Pennsylvania, control: non - transduced T cells. TCR avidity and specificity data not shown, available in IMA204 presentation on Immatics website. COL6A3 exon 6 prevalently expressed at high target density in tumor stroma across many solid cancers I MA2 0 4
ACTallo® – Our Next - generation Off - the - shelf TCR - T 74
ACTallo® – Immatics’ llog n ic ll h ra y roach • Off - the - shelf cell therapy , no need for personalized manufacturing reduced logistics and time to application • Potential for hundreds of doses from one single donor leukapheresis lower cost of goods • Use of healthy donor material provides standardized quality and quantity of starting material • Strategic collaborations combining Immatics’ proprietary ACTallo® platform with Bristol Myers Squibb’s next - gen technologies and Editas Medicine’s CRISPR gene editing technology to develop next - gen allogeneic γδ TCR - T/CAR - T programs 75 A C T allo® γδ T cell Cell Engineering (gene editing & armoring) γδ T cell Collection from Healthy Donor Expa n sion O f f - the - s h elf Products Patient T r e a tme n t
Why γδ c lls? γδ T cells Are Well Suited for an Off - the - shelf Cell Therapy Approach 76 γδ T cells x are abundant in the peripheral blood x show intrinsic anti - tumor activity x naturally infiltrate solid tumors & correlate with favorable prognosis x are HLA - independent, thus do not cause graft - vs - host disease in allogeneic setting x can be expanded to high numbers in a cGMP - compatible manner x can be effectively redirected using αβ TCR or CAR constructs In vitro anti - tumor activity 0 4 8 1 4 4 1 9 2 0 5 1 0 1 5 9 6 H o u r s ) + P F R - S 0 2 U ( h t w o r G d l o F T u m o r c e lls o n ly T ce lls ( N T ) T c e lls ( N T ) T c e lls IM A 2 0 3 T C R + T ce lls IM A 2 0 3 T C R + γδ T cells (control) + tumor cells tumor cells only αβ T cells (control) + tumor cells γδ T cells TCR + + tumor cells αβ T cells TCR + + tumor cells A C T allo® 0 . 00 1 0 . 0 1 0 . 1 1 1 0 10 0 100 0 1000 0 10000 0 100000 0 0 5 10 15 20 25 Day Fold expansion of T cells Expa n sion Fold - growth (target - positive tumor cells)
Corporate Information & Milestones 77
Harpreet Singh Chief Executive Officer Co - Founder >20 yrs biotech experience Arnd Christ Chief Financial Officer >20 yrs biotech experience (InflaRx, Medigene, NovImmune, Probiodrug) Carsten Reinhardt Chief Development Officer >20 yrs pharma & biotech experience (Micromet, Roche, Fresenius) Cedrik Britten Chief Medical Officer >15 yrs pharma & biotech experience (GSK, BioNTech) Rainer Kramer Chief Business Officer >25 yrs pharma & biotech experience (Amgen, MorphoSys, Jerini, Shire, Signature Dx) Steffen Walter Chief Operating Officer Co - Founder Immatics US >15 yrs biotech experience Edward Sturchio General Counsel >15 yrs pharma & biotech experience (Abeona Therapeutics, AAA, Novartis, Merck, Schering) Jordan Silverstein Head of Strategy >10 yrs biotech experience (InflaRx, AAA) Toni Weinschenk Chief Innovation Officer Co - Founder >15 yrs biotech experience Experienced Global Leadership Team Across Europe and the US Corporate 78
Strong, Focused and Highly Integrated Trans - Atlantic Organization 79 Houston, Texas ~205 FTEs Cell therapy development & manufacturing Munich, Germany ~85 FTEs Various operating functions Tübingen, Germany ~255 FTEs Target & TCR discovery and TCR Bispecifics d ev elopm e nt Corporate FTEs as of June 30, 2024
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